Depression in mentally retarded individuals is not uncommon and usually is treatable. However, studies of the diagnosis and treatment of psychiatric illnesses in general and depression specifically in this population are relatively rare. Although Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria can be applied to mildly and moderately retarded individuals, the diagnosis of depression in those with intelligence quotients below 35 is challenging. However, the diagnosis of depression in the latter group is possible using modified criteria emphasizing observational data. Criteria include symptoms such as sadness, irritability, decreased social interaction, regression of skills, sleep disturbances, diurnal variation, and aggression. Furthermore, there is a growing body of evidence that antidepressant treatments, especially administration of selective serotonin reuptake inhibitors, are effective in treating depression in mentally retarded patients. This article reviews numerous studies elaborating on the diagnosis, phenomenology, and treatment of depression in mentally retarded individuals.