Aims -. To review the factors which are relevant for a correct evaluation of the costs of antidepressant drug treatment and to report the results of the studies on the efficacy, tollerability and costs of the most utilized antidepressants (tricyclics and SSRI). Methods - We reviewed the international literature concerning both with comparative studies on efficacy, tollerability and safety of tricyclics and SSRI and with studies of pharmacoeconomics that have focused on the costs of depression and of different antidepressant treatments. Results - Depression involves high costs, especially if indirect costs are considered. Comparative studies indicate a substantial equivalence of efficacy between tricyclics and SSRI, but a better tolerability of the latters. The few studies of pharmacoeconomics that have evaluated different antidepressant drugs indicate that a treatment with SSRI involves lower costs as compared with tricyclics. These results are due to the higher indirect costs (compliance, drop-out for side-effects, work loss, etc.) of tricyclics. Conclusions - A correct economic evaluation of an antidepressant drug treatment should consider both direct and indirect costs. Available studies indicate that SSRI involves lower costs as compared with tricyclics; however in order to confirm these results more studies of pharmacoeconomics are needed with experimental designes (longitudinal studies) taking into account the outcome of patients treated in routine clinical practice.