Hepatic dysfunction is a commonly recognized complication of sickle cell crisis. The cause of hepatic compromise is usually made evident from physical examination, clinical history, laboratory testing, and noninvasive imaging. There are occasions when liver biopsy is required to define the etiology of the hepatic dysfunction. Liver biopsy during acute sickle hepatic crisis can result in hemorrhage and death. Careful consideration of alternatives must be explored prior to performing liver biopsy on a patient with acute sickle hepatic crisis. If biopsy cannot be delayed, close hemodynamic monitoring of the patient postbiopsy is essential.