Communities of Practice (CoPs) are emerging as a promising strategy for building sustainable peer networks that ultimately can function as systems of support within a local region. The content of this guide is based upon the work of the Power of Discovery: STEM² Initiative. In addition to general descriptions of design and implementation strategies and considerations, it also contains practical examples of how a CoP can look and feel across diverse regional contexts. This guide is intended to serve as a resource for those interested in building a community of practice within or across organizations, communities, and/ or regions.