The treatment of depression in the elderly population needs a thorough and careful work-up and an aggressive therapeutic approach. Any treatment initiative in this population often becomes difficult because of accompanying physical illness, concomitant medication, possible degenerative changes in central nervous system and age-related altered metabolic status. Despite unevenness in research findings, pharmacological treatment remains the mainstay of management of depression among elderly people. Currently available antidepressants, although effective, are problematic because of the increased vulnerability of the elderly to side effects. Recent research efforts to improve the efficacy and safety of drug treatment of depression resulted in development of reversible and selective monoamine oxidase inhibitors of the isoenzyme A (RIMA), with antidepressant efficacy comparable to tricyclic antidepressants and newer generation antidepressants. RIMAs include moclobemide, brofaromine, toloxatone and cimoxatone. Moclobemide is the most investigated available RIMA for therapeutic use at present. Its absorption and disposition in elderly individuals do not differ significantly from those in young healthy volunteers and depressed patients. The results of present clinical studies show that, in elderly depressed patients, moclobemide is at least as effective as other antidepressants. Its particular advantage is, however, that it is as well tolerated in elderly people as in younger people. There are only few significant adverse events, and they are generally less frequent and less severe than those with TCAs. An additional attribute of moclobemide seems also to be its beneficial effect on cognitive functions.