The introduction of the SSRIs has significantly transformed the pharmacological treatment of a range of psychiatric disorders. In particular, individuals affected by depression, panic disorder, obsessive-compulsive disorder and social phobia have benefited substantially from their use. Compared with the previous generation of psychotropic drugs, SSRIs offer an improved tolerability to therapy while maintaining a high level of efficacy. Nevertheless, despite these advantages, not all patients benefit from treatment; an appreciable proportion do not respond adequately, while others may react adversely. This necessitates a review of the initial treatment choice, often involving extended periods of illness while a more suitable therapy is sought. Such a scenario could be avoided were it possible to determine the most suitable drug prior to treatment.Several factors are postulated to influence outcome of drug therapy; most recently, pharmacogenetic studies have demonstrated a significant influence of genetic mechanisms on the efficacy of clinically prescribed drugs. This contribution, which is primarily a reflection of alterations in genes that encode drug-metabolising enzymes, drug receptors, transporters and second messengers, may be pertinent to the success of SSRI therapy.Attesting to this potential, studies to elucidate the influence of genetic processes on SSRI efficacy now represent a major focus of pharmacogenetics research. Current evidence emerging from the field suggests that gene variants within the serotonin transporter and cytochrome P450 drug-metabolising enzymes may bear a particular importance, though further corroboration of these findings is still warranted. At the same time, it appears likely that further key participating genes remain to be identified. By comprehensively delineating these genetic components, it is envisaged that this will eventually facilitate the development of highly sensitive protocols for individualising SSRI treatment.