Diuretics are important drugs in the treatment of arterial hypertension, congestive heart failure, the nephrotic syndrome, and other clinical conditions. With diuretic treatment, reduction of both morbidity and mortality has been clearly shown in those conditions. However, a recent meta-analysis showed an increased risk for renal cell carcinoma in patients treated with diuretics. We summarize and critically review data from studies examining the association between diuretic use and renal cell carcinoma. In general, in many clinical conditions, the reduction of mortality with diuretic therapy outweighs a potential risk of renal cell carcinoma. However, in certain conditions, alternative medical treatment should be considered.