Late-life depression (LLD) is a common and typically recurrent illness that is often unrecognized and under-treated. It is associated with significant co-morbidities and poor health outcomes. Antidepressants are typically used as a first-line treatment for LLD. We performed a systematic review of the English literature (1996 to August 2007) and present results relevant to the efficacy of antidepressants in acute and maintenance pharmacotherapy of LLD, the predictors of LLD treatment outcomes and pharmacological strategies for non-remission. There is a consensus in the literature that the goal of treatment should be remission. Although antidepressants can be categorized into several classes based on their putative mechanisms of action, there is no consistent evidence that antidepressants from different classes are associated with different rates of remission of LLD. After achieving remission, the evidence supports a beneficial role of maintenance pharmacotherapy in reducing the rate of recurrence of LLD for at least 2 years. There are reports of a number of possible augmentation and switching strategies that can be used when LLD remission is not attained. However, none of these various strategies has been studied rigorously in patients with LLD as yet. Overall, the current literature is adequate for guiding acute and maintenance pharmacotherapy of LLD but further research is urgently needed to guide clinical strategies in non-remission.