We report the case of attempted suicide by a 30-year-old man who had significant cognitive deficits that developed after at least three years of polysubstance use with cannabis, methylenedioxymethamphetamine (MDMA, "ecstasy") and cocaine. The patient reported increasing difficulties in his professional and interpersonal life which may have been associated with his cognitive dysfunction caused by his poly-drug use. In this setting, the patient complained of increasing symptoms of depression, including feelings of hopelessness and helplessness, and multi somatic complaints (based on DSM-IV criteria). These depressive symptoms led to the development of active suicidal ideation and ultimately to a suicide attempt. We propose that the patient's cognitive deficits resulted directly from his polysubstance use and contributed to his depression, suicide attempt and current serious suicidal ideation.