Developing research suggests that the co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is a significant clinical concern across first responder populations. This comorbidity is difficult to treat and marked by a more costly, complex, and chronic clinical course when compared to either disorder alone. Significant associations between PTSD/AUD comorbidity and various psychological, behavioral, and physical health outcomes among first responder samples have been documented. This chapter provides a theoretical framework and empirical review of the literature relevant to PTSD/AUD in the context of firefighter, police, and other first responder populations (e.g., emergency medical technicians). Future directions, utilizing varied methodologies and assessment tools, and focusing upon varied first responder populations are enumerated to build upon this preliminary, yet clinically meaningful, empirical foundation. This research domain has great potential to inform specialized, evidence-based clinical care for first responders.