Co-occurrence of substance use disorders (SUDs) and posttraumatic stress disorder (PTSD) is extremely common and is associated with elevated dropout and relapse rates. Given that PTSD/SUD co-occurrence rates among veterans have been found to be as high as 55-75%, it is important to identify mechanisms that may affect the interplay of both disorders. Emotion dysregulation (ED) presents a candidate mechanism that may underlie poor treatment response in co-occurring PTSD/SUD. This article proposes a transdiagnostic emotion regulation framework that considers ED conceptualized as a combination of low ability to tolerate emotional distress (low distress tolerance) and difficulties in the goal-directed use of emotion regulation strategies as a key risk factor in co-occurring PTSD/SUD. The authors review empirical findings from self-report and laboratory-based studies of ED in PTSD. They describe psychological explanations of the emotion-substance relationship and review studies documenting ED in SUDs and in co-occurring PTSD/SUD. The literature on ED in PTSD/SUD suggests that (a) patients with PTSD may resort to substances to cope with trauma-related symptoms due to ED, and (b) ED may maintain SUD symptoms and interfere with psychological treatment. Longitudinal studies on bidirectional relationships between ED and substance use in PTSD are needed, particularly research examining the course of ED in PTSD patients who use substances versus those who do not.