Renal and hepatic diseases have a significant impact on the plasma concentration profiles and the dose requirements for almost all drugs. This paper reviews the effect of these diseases and their associated physiological derangements on the pharmacokinetics of fluoxetine and norfluoxetine. Metabolic studies of fluoxetine in man show that more than 70% of the radiolabelled compound is excreted in the urine. Most of the urinary radiolabelled products are metabolites and not the parent compound nor its active metabolite, norfluoxetine. Cirrhosis of the liver significantly reduces the clearance of fluoxetine and norfluoxetine, but mild, moderate, or severe renal dysfunction does not affect fluoxetine or norfluoxetine pharmacokinetics. Daily administration of fluoxetine, 20 mg, for more than 2 months to renally impaired, depressed patients (who require haemodialysis) produces steady-state fluoxetine and norfluoxetine plasma concentrations that are comparable to the concentrations in depressed patients with normal renal function. Renal function is not an important determinant of the steady-state concentrations of fluoxetine or norfluoxetine, though the concentrations may be higher in patients with significantly impaired liver function.