BACKGROUND: Depression is one of the leading indications for using Complementary and Alternative Medicine (CAM). This paper reviews the evidence of efficacy of different types of CAM in depression with the aim of identifying the highest level of evidence. METHODS: We conducted literature searches restricted to the English language for studies on CAM as monotherapy in depression. All papers were reviewed by two researchers and the evidence was ranked according to a widely referenced hierarchy of evidence. RESULTS: 19 papers formed the final review. We found Grade 1 evidence on the use of St. John's wort, Tryptophan/5-Hydroxytryptophan, S-adenosyl methionine, Folate, Inositol, Acupuncture and Exercise in Depressive disorders, none of which was conclusively positive. We found RCTs at the Grade 2 level on the use of Saffron (Herbal medicine), Complex Homoeopathy and Relaxation training in Depressive disorders, all of which showed inconclusive results. Other RCTs yielded unequivocally negative results. Studies below this level yielded inconclusive or negative results. LIMITATIONS: Searches were restricted to the English language. Our list of CAM approaches may not have been comprehensive. We excluded studies on the use of CAM as an adjunctive treatment and this review aimed to identify only the highest level of evidence. CONCLUSIONS: None of the CAM studies show evidence of efficacy in depression according to the hierarchy of evidence. The RCT model and the principles underlying many types of CAM are dissonant, making its application in the evaluation of those types of CAM difficult. The hierarchy of evidence we used has limited utility in grading trials of CAM.