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While Dishonored 2 is not really an open-world game, you're not without choices. Mostly, this comes down to how badly you hurt the people you meet on your mission to reclaim the throne. In game, your tendency toward stabbiness is measured in Chaos — Low Chaos and minimal murder lead to a more optimistic ending, while High Chaos and a trail of bodies leads to the cynical ending. Visually, this is represented by the number of bloodflies you see in the environment (since bloodflies love corpses).
Unlike the first Dishonored with its black and white endings, the math of the ending you see in Dishonored 2 is not a simple tallying of body count. It's a lot more like calculus. The choices you make — who gets killed, who gets knocked out, who gets shipped to Abu Dhabi (see Dust District) — are all interwoven into the details of your specific ending. We'll provide you details throughout this guide so you can choose where to use cunning and where to use your sword.
Chaos and mission targets

Low Chaos
Low Chaos is tied to the stealthy approach. However, unless you're going for the Ghostly ("finish an entire mission without being spotted") or Shadow ("finish the [entire] game without being spotted") achievements, Low Chaos doesn't have to mean you're never noticed. It just means that you don't kill any more than you absolutely need to.
The easiest way to avoid the temptation to murder and to avoid people trying to murder you is to avoid being seen. Importantly, even if you're not murdering and not being noticed, you can still use non-lethal attacks — knocking people out is not Chaos-inducing (this applies to the game only and should not be considered legal advice).
High Chaos
It's easiest to think of the High Chaos approach as the "I have a sword and gun, it'd sure be a shame not to use them" philosophy. High Chaos is, frankly, easier. You will still have to avoid being spotted by large groups of enemies — it's very easy to get overwhelmed and killed — but the "damn the consequences" approach is freeing and will not require you to look over your shoulder constantly. And watching those sweet, sweet murder animations makes this style well worth the moral baggage and cynical ending.
Mission Targets
Your journey to right wrongs will take you through a ever-deepening conspiracy of characters. The Low and High Chaos philosophies above apply to these mission targets as well.
The context of the level and hints provided by notes or overheard dialog will give you options on dealing with your targets. Throughout this guide, we'll provide you with all of the methods to handle each challenge.
Low versus High Chaos
Polygon's Dishonored 2 guide is written starting from a stealthy, Low Chaos approach. There's a reason for this: If you don't care about blood on your hands, you can just replace the word "avoid" with the word "stab" and the directions this guide provides will still get you to your destination.
Stealthiness and avoidance are useful habits regardless of your style of play because they keep you from getting outnumbered. As you play, the choice is up to you whether to slip past, knock out or decapitate the various enemies we mention in this guide.
Unless you're going for the Ghost or Shadow achievements mentioned above or the Alternative Approach ("finish an entire mission with no casualties") or Clean Hands ("complete the game without killing anyone") achievements, don't get discouraged if you get detected or accidentally cut someone's leg off (we've all been there). Your actions are graded on sliding scale. A couple murders aren't going to plunge you into the darkest timeline.
Collectibles, literature and loot
Each mission in Dishonored 2 is full of story context, collectibles, upgrades and cash. As a rule, we're not going to point out every drawer, cabinet and closet that has an apple, a few coins or health elixirs inside. Get in the habit of checking everywhere. Open every drawer and check every room, even if that room isn't on the direct path to your destination. Take everything that's not nailed down.

While looking for things to pocket, you'll also encounter newspapers, books and notes. These provide fascinating background and texture to the larger world of Dishonored 2, as well as hints about ways to complete your objectives and side missions. We highly recommend at least skimming anything you come across.
Markers for both runes and bonecharms show up on your screen when you equip the heart — an in-game device we won't get into here — and that makes them easy to find.
For a complete location guide to the collectibles listed below, check out Polygon's Dishonored 2 collectibles guide.
Runes

Runes upgrade and expand your Outsider powers. If you choose to reject the Outsider's offer of supernatural powers (to earn the Flesh and Steel achievement or because you're a masochist), you can probably ignore runes. Otherwise, runes and the powers they open up make the game both easier and more exciting.
Bonecharms

Bonecharms, the more powerful black bonecharms and corrupt bonecharms serve as buffs to Corvo and Emily's abilities — both supernatural and mundane. They do things like let you hold your breath longer, make elixirs more effective or improve your melee abilities. Unlike the other two, corrupt bonecharms come with a cost — some detriment to offset the benefit — so read the description carefully when choosing what to equip.
Using runes (and the Outsider's mark), you can develop the ability to craft your own bonecharms and not rely solely on finding them in the world. To craft your own bonecharms, you'll need raw whalebone, which you'll find in lootable locations in pretty much every mission (see our note above about grabbing everything that's not nailed down). You can also turn your unspent runes into bonecharms, assuming you have any.
Blueprints

The other important (and useful) collectibles you'll encounter are blueprints, which allow you to do things like increase your crossbow's damage, run more quietly or, usefully, equip more bonecharms. Blueprints don't provide an immediate benefit, but collecting them will open up equipment upgrade options when you visit the various black markets you find along your way.
Blueprints are squirreled away in (usually) hard-to-reach locations that don't show up on your HUD. You can find all of the game's blueprints in Polygon's Dishonored 2 collectibles guide.
Paintings

Paintings were included in our collectibles guide for two reasons: they're listed on the end-of-mission report, and they will get you the Art Collector achievement. Even if neither of those things interest you, paintings are worth at least a little of your time because they earn you 150 coins for every one you steal. You can spend those coins on the upgrades you unlock when you collect blueprints.
Also, they have amazing names.
Look, what we're saying is, go read Polygon's full Dishonored 2 collectibles guide. It's super useful.