In assessing the efficacy and the safety of a new drug, randomized clinical trials represent the standard scientific method. The selection of the best response variables in a clinical trial of a treatment in congestive heart failure patients is often not straightforward; the primary end point of a trial should be clinically relevant, directly related to the primary goal of the trial, and with favorable distributional properties. All-cause mortality is undoubtedly the most unbiased endpoint, but there is interest both in assessing cause-specific mortality and hospitalization rate and in evaluating 'soft' endpoints (functional status, exercise tolerance); the latter, in fact, are clinically relevant and potentially more useful in mild heart failure patients. Physiopathologic variables (e.g. left ventricular function) could provide information on drug action mechanism. In this paper, several recent large clinical trials are reviewed and the advantages and drawbacks of the response variables used, are analyzed.