Objectives: To evaluate drug treatment of functional dyspepsia (including Helicobacter pylori) and provide guidelines for future trials based on a critical systematic overview of published studies. Methods: Data sources were a Medline search for articles published in English going back to 1966 and a manual search of four GI journals going back to 1980. Original randomized, double-blind, placebo-controlled trials were selected that enrolled at least 20 patients. Using a standardized, pretested data extraction form, studies were evaluated independently by two observers for study design, outcome measures, and results. Results: Fifty two eligible studies were evaluated. Many studies suffered from important weaknesses in study design and execution. Only five studies used previously validated outcome measures. Conclusions: Because of suboptimal design and/or unclear presentation of the data, none of the trials provided unequivocal evidence that there is efficacious therapy for the treatment of functional dyspepsia.