The use of diuretics for the treatment of sodium retention in congestive heart failure was evaluated. Particular focus was given to the altered renal response to diuretics in patients with heart failure and adverse responses to diuretic therapy. Highlighted information included historical aspects of the development of diuretics, mechanisms of sodium retention, the physiologic and clinical response to diuretics, and the altered pharmacokinetics and pharmacodynamics of diuretics in congestive heart failure. Despite more than 60 years of empiric diuretic use in heart failure, the actual database regarding the long-term efficacy, adverse effects, and altered mortality outcome in heart failure is relatively small. Existent pharmacokinetic and pharmacodynamic data are typically not collected within the context of heart failure efficacy trials. In addition to altered electrolyte transport and total-body electrolyte depletion, diuretics may be associated with adverse neurohormonal activation. Thus, guidelines for acute and long-term therapy with diuretics in heart failure remain somewhat empiric. Diuretics will remain a mainstay for the treatment of edema in congestive heart failure but must be accompanied by moderate sodium restriction. However, large clinical trials of diuretics would be necessary to demonstrate that improved clinical efficacy with edema reduction is not offset by adverse effects, which include electrolyte depletion, ventricular arrhythmias, and subsequent increased mortality.