Gemtuzumab ozogamicin (Mylotarg) therapy may cause sinusoidal obstruction syndrome (SOS), the mechanism of which probably involves targeting of CD33+ cells in the sinusoids of the liver, activation of stellate cells, damage to sinusoidal endothelial cells, sinusoidal vasoconstriction, and ischemic hepatocyte necrosis. The clinical manifestations of this liver injury are hepatomegaly, weight gain, ascites, jaundice, and elevation of serum aminotransferase enzymes. An approach to patient management includes being certain that SOS is the correct diagnosis; ensuring that liver blood flow is optimized; and managing the accumulation of fluid in the peritoneal cavity, pleural spaces, and pulmonary interstitium. Currently, there is no specific therapy that is directed at the sinusoidal pathology caused by gemtuzumab ozogamicin. There are, however, several rational therapies that might be tried in patients who exhibit adverse prognostic signs early in the course of SOS. There is also considerable ongoing hepatology research dealing with stellate cell and sinusoidal endothelial cell biology and regulation of sinusoidal blood flow that can be brought to bear on this problem in the future.