Major depressive disorder is common in the elderly and is associated with significant morbidity and disability, as well as increased risk of mortality. Extensive literature is extant examining the efficacy and tolerability of the earlier antidepressants but there are comparatively fewer trials examining the newer antidepressants, the so-called 'third generation' antidepressants with a variable mode of action. This article reviews the literature published in the past 10 years on the efficacy and tolerability of the new antidepressantsescitalopram, venlafaxine, duloxetine and mirtazapine -used in treating depression of old age. There are no published data for the newly released desvenlafaxine in the elderly population. Due to the limited number of published trials and their highly heterogeneous nature, specific treatment recommendations for depression in older people are not supported by solid empirical evidence. Clearly, further studies on the management of depression in older people are needed in order to develop reliable and practical guidelines. J Pharm Pract Res 2010; 40: 58-64.