The potential impact of sleep and sleep disorders on stress responses has received increasing interest particularly in the context of Post-traumatic Stress Disorder (PTSD). This review aims at synthesizing current evidence concerning the link between trauma exposure, sleep, emotional regulation and stress. In the last decades, experimental investigations suggested a critical role of sleep on emotional memory formation and emotional reactivity; similarly, animal and human studies highlighted the relations between sleep and fear responses, supporting the notion that sleep disturbance plays an important role in PTSD-relevant processes such as fear learning and extinction. Although some crucial aspects of these interactions need further clarification, convincing evidence now suggests a complex physiological interaction of stress response and sleep. In the context of trauma-related disorders, sleep alterations have been suggested as core symptoms as well as risk and prognostic factors; importantly, sleep may also represent an important therapeutic target in mental health. However, evidence accumulated so far points to sleep disturbance as a marker not only of PTSD, but also of increased vulnerability to maladaptive stress responses. Novel models conceptualize sleep disturbance as a modifiable, transdiagnostic risk factor for mental disorders, with important theoretical and clinical implications.