Diuretics are among the most commonly used drugs. They increase the rate of urine flow and sodium excretion and are used to induce negative fluid and sodium balance in a variety of clinical situations, including hypertension, heart failure, renal failure, nephrotic syndrome, and cirrhosis. It is essential for clinicians to understand the mechanism of action of various diuretics to be able to maximize the efficacy of these agents when used as monotherapy and in combination with agents that have different targets of action in the kidney. The pharmacology of commonly used diuretics and the renal anatomy and physiology relevant to diuretic effects are reviewed.