The systemic complications of nephrotic syndrome are responsible for much of the morbidity and mortality seen with this condition. This review discusses the causes for the hypoalbuminemia and the associated metabolic abnormalities of the nephrotic syndrome. No unifying hypothesis exists for the induction, maintenance, and resolution of nephrotic edema. In view of the wide spectrum of renal diseases leading to the nephrotic syndrome, more than a single mechanism may be responsible for the renal salt retention in these diverse conditions. Although hypoalbuminemia may be important, especially when plasma oncotic pressure is very low (serum albumin < 1.5 to 2.0 g/dL), primary impairment of salt and water excretion by the nephrotic kidney appears to be a major factor in pathogenesis of the edema. However, the decreased serum albumin and/or oncotic pressure seen with nephrotic syndrome is a major contributing factor to the development of the hyperlipidemia of nephrotic syndrome. Patients with unremitting nephrotic syndrome should be considered for combined dietary and lipid-lowering drug therapy. Urinary losses of binding proteins lead to the observed abnormalities in the endocrine system and in trace metals, and urinary losses of coagulation factors contribute to the hypercoagulable state. At present, selective renal venography is recommended when the suspicion of renal vein thrombosis is justified by clinical presentation. The impact on renal function caused by treating asymptomatic chronic renal vein thrombosis is undetermined, but anticoagulation for chronic renal vein thrombosis is associated with relatively few complications.