Smoking is a known risk factor for cardiovascular diseases, cancer, and several other health problems. It is the number one preventable cause of death in modern countries. The first evidence that smoking may be a renal risk factor was published in 1978. Since then, several studies documented that smoking is nephrotoxic in patients with diabetic and non-diabetic renal disease. Data from the Multiple Risk Factor Intervention Trial indicate that smoking even increases the renal risk in the general male population: an increased relative risk for end-stage renal failure (ESRF) was found for smokers as compared to non-smokers (up to 1.69 for heavy smokers). Several potential mechanisms of smoking-induced renal damage have been discussed, e.g. increase in blood pressure, alteration of intrarenal hemodynamics, as well as activation of the sympathetic nerve, the renin-angiotensin and the endothelin systems. The pathomechanisms are, however, only partly understood. Once ESRF has become established, the failure to discontinue smoking adversely affects the prognosis of patients on renal replacement therapy, mainly by increasing the risk of cardiovascular complications. Discontinuation of smoking has been shown to improve both renal and cardiovascular prognosis in the renal patient and is probably the single most effective measure to retard progression of renal failure.