Abstract: With the increased emphasis on practising evidence based medicine, clinicians need to be able to select the best evidence available on which to base their practice. A problem exists in the ways in which primary care clinicians use antidepressants in the treatment of depression. General practitioners (GPs) have been criticised on several counts, including; drug choice, inadequate dosage of drug and inadequate duration of treatment. GPs have answered these criticisms by pointing out that most of the research that has shown efficacy of drug treatments for depression has been conducted using patients treated in secondary and/or tertiary care settings. The vast majority of depressive disorders however are seen and treated wholly in primary care settings with depressive disorders representing a very large proportion of primary care clinicians' workload. A number of studies have indicated that in general practice, depressed patients have milder shorter illnesses than psychiatric samples, and that major depressive disorders in primary care patients have different causation, pathophysiology and natural history than those of psychiatric inpatients and/or outpatients. There is thus a need to assess the existing evidence regarding the efficacy and tolerability of all antidepressant agents specifically administered to a primary care clinical sample. The present authors are currently undertaking a systematic review within the Cochrane Collaboration (Depression, Anxiety & Neurosis group), in order to provide valid and precise estimates of the efficacy and tolerability of all antidepressant agents, (comparing drugs, drug with placebo, and drug with physician's usual care) in the treatment of depressive disorders in primary care. This paper presents any interesting preliminary findings, and discusses the methodological and practical implications of our results in the light of previous primary and secondary research concerned with antidepressant prescribing.