The vascular lesions of the liver described in association with drug and toxic substance exposure are reviewed, with special reference to the abnormalities of the following: (1) the hepatic venous efferent system (ie, large and small hepatic vein obstruction); (2) the sinusoids (ie, sinusoidal dilatation, peliosis, perisinusoidal fibrosis); (3) the portal vein and its branches; and (4) the hepatic arterial tree. Drug-induced vascular tumors of the liver and vascular changes observed within nonvascular tumors of the liver are also envisaged. Finally, the pathophysiologic mechanisms of all these lesions are considered. The awareness of this type of hepatotoxicity and the knowledge of its epidemiology seem to be essential for both its early detection and prevention.