Depression is one of the most frequent comorbid psychiatric disorders in Alzheimer's disease and other dementias, and is associated with poorer quality of life, greater disability in activities of daily living, a faster cognitive decline, a high rate of nursing home placement, relatively higher mortality and a higher frequency of depression and burden in caregivers. Depression in Alzheimer's disease is markedly under-diagnosed and most patients with depression are either not treated or are on subclinical doses of antidepressants. Recent randomized controlled trials have demonstrated the efficacy of sertraline and moclobemide to treat depression in Alzheimer's disease. Other psychoactive compounds may be useful as well, but careful consideration must be given to potentially serious side effects.