1. 13 years after the discovery of endorphins, the relationships between these peptides and mental illness remain unclear. 2. Current concepts are controversial and convincing hypotheses have not been elaborated yet. 3. Endorphin measurements in CSF or serum of psychiatric patients did not strongly support that schizophrenia or depression is related to a deficit or an excess of these peptides. Moreover, treatment with endorphins or opiate antagonists did not result in a distinct change of psychiatric symptoms. Recently, research focused on the relationship between endorphins and addictive behavior, but substantial evidence for clinical relevance is still missing. 4. The physiological relevance of many newly discovered endorphins is barely known and several subtypes of the opiate receptor have been found. Thus, it will still require a substantial effort in basic and clinical studies before, if at all, endorphins turn out to be helpful in the treatment of mental illness.