Long known for its anti-nociceptive effects, the opioid β-endorphin is also reported to have rewarding and reinforcing properties and to be involved in stress response. In this manuscript we summarize the present neurobiological and behavioral evidence regarding the role of β-endorphin in stress-related psychiatric disorders, depression and PTSD. There is existing data that support the importance of β-endorphin neurotransmission in mediating depression. As for PTSD, however, the data is thus far circumstantial. The studies described herein used diverse techniques, such as biochemical measurements of β-endorphin in various brain sites and behavioral monitoring, in two animal models of depression and PTSD. We suggest that the pathways for stress-related psychiatric disorders, depression and PTSD, converge to a common pathway in which β-endorphin is a modulating element of distress. This may occur its interaction with the mesolimbic monoaminergic system and also by its interesting effects on learning and memory. The possible involvement of β- endorphin in the process of stress-related psychiatric disorders, depression and PTSD, is discussed.