The efficacy of pharmacological interventions used to treat canine atopic dermatitis, excluding fatty acid supplementation and allergen-specific immunotherapy, was evaluated based on the systematic review of prospective clinical trials published between 1980 and 2002. Studies were compared with regard to design characteristics (randomization generation and concealment, masking, intention-to-treat analyses and quality of enrolment of study subjects), benefit (improvement in skin lesions or pruritus scores) and harm (type, severity and frequency of adverse drug events) of the various interventions. Meta-analysis of pooled results was not possible because of heterogeneity of the drugs evaluated. Forty trials enrolling 1607 dogs were identified. There is good evidence for recommending the use of oral glucocorticoids and cyclosporin for the treatment of canine atopic dermatitis, and fair evidence for using topical triamcinolone spray, topical tacrolimus lotion, oral pentoxifylline or oral misoprostol. Insufficient evidence is available for or against recommending the prescription of oral first- and second-generation type-1 histamine receptor antagonists, tricyclic antidepressants, cyproheptadine, aspirin, Chinese herbal therapy, an homeopathic complex remedy, ascorbic acid, AHR-13268, papaverine, immune-modulating antibiotics or tranilast and topical pramoxine or capsaicin. Finally, there is fair evidence against recommending the use of oral arofylline, leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists.