Individuals diagnosed with posttraumatic stress disorder (PTSD) commonly experience complex psychosocial and interpersonal circumstances. Fortunately, research suggests that cognitive processing therapy (CPT) is safe and effective to deliver to patients experiencing many of these circumstances, including those at elevated risk for suicide, exposure to violence, housing instability, and criminal–legal involvement. To navigate these complex circumstances, research and clinical frameworks encourage providers to use careful assessment, thoughtful case conceptualization, and an adaptable approach to care. This chapter provides an overview of the research regarding delivery of CPT in the context of specific challenging psychosocial and interpersonal circumstances, followed by a consolidation of clinical recommendations for each circumstance to help clinicians deliver CPT for these patients. While there may be changes to the scaffolding of CPT, the core structure and tenants of CPT are largely unchanged for patients in the context of complex psychosocial and interpersonal circumstances. Through both reduction of PTSD symptoms and acquisition of generalizable skills, CPT can assist patients in addressing both trauma symptoms and navigating challenging circumstances.