Several drugs, or categories of drugs, listed by the WHO and other writers and used in the treatment of chronic disease, are consistently associated with weight gain as a side effect and considered 'obesogenic'. The extent to which they may contribute to the multifactorial process behind obesity is not well documented. We systematically reviewed papers from Medline 1966-2004, Embase 1980-2004, PsycINFO 1967-2004, and Cochrane Register of Controlled Trials, to determine the effect on body weight of some drugs that are believed to favour weight gain. We included randomized controlled studies of adult participants (>18 years) prescribed a drug considered obesogenic, that compared the 'obesogenic' drug with placebo, an alternative drug or other treatment, and that had a duration of at least 3 months: 43 studies totalling 25,663 subjects met these criteria. The main objective of the majority of studies was to compare the efficacy and safety of drug therapy, with weight change recorded under safety outcomes; weight change was a primary outcome measure in only six studies. There was evidence of weight gain for all drugs included, up to 10 kg at 52 weeks. Differences in dosage, patient population, duration of treatment and dietary advice make generalization of the results difficult. Data on body weight are often not recorded in published clinical trials or is reported in insufficient detail. This side-effect has potentially serious consequences, and should be mentioned to patients. Weight management measures should be routinely considered when prescribing drugs known to promote weight gain. Future clinical trials should always document weight changes.