This guide contains a foreword and five chapters. The chapters are modular and do not need to be read in order. Each chapter is designed to be brief and accessible to health care providers, health care system administrators, community members, and others working to meet the needs of individuals at risk for, experiencing, or recovering from a substance use disorder and/or mental illness. The goal of this guide is to review the literature on treating substance misuse and substance use disorders in the context of first-episode psychosis, distill the research into recommendations for practice, and provide examples of the ways that these recommendations can be implemented by first-episode psychosis treatment programs.