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The setup necessary for building ES6 apps is determined by the amount of cross-platform compatibility you wish to give. Most of ES6 is already supported by the latest versions of Chrome, Firefox, Edge, and Node.js, so if you're just targeting these newer runtimes, you can start using it right now.For further details about which runtimes support which features, you can consult the ES6 compatibility table.
I've tried to cover some of the most important new changes, but there are many other cool new features in ES6 that I don't have space to cover in this article. For more information, you can browse a quick overview of the new features on es6-features.org, read a more detailed introduction in the Exploring ES6 book, and, for even more in-depth details, read the ECMAScript 2015 Language Specification.
Fortunately, there's a project called Babel which allows you to convert your ES6 code into ES5 code. This means that you can still write code in ES6 while developing web applications that anybody with an ES5-compliant browser can use. It takes some effort to figure out how to set everything up the first time, so I've included a step-by-step guide below to help you get started more quickly.