The articles selected for this special issue address the complexity of general clinical practice with particular attention to co-occurring problems and challenging risk behaviors. In some cases, the co-occurring problem overlaps with a medical domain such as Lyme disease, diabetes, or somatic concerns of unexplained medical origin. Other articles bring the reader up to date on current trends in the assessment or treatment of risk behaviors in children, adolescents, and couples. Throughout this special issue, the articles highlight the utility of evidence-based tools and assessment. It is the author’s hope that this special issue may spark the curiosity of the general practitioner to utilize screenings, conceptualize challenging cases in new ways, and further explore continuing education to broaden the scope of assessment or treatment in these domains. (PsycInfo Database Record (c) 2022 APA, all rights reserved)