Methamphetamine has been recognized as a common cause of acute toxic hepatitis in adults with clinical and histologic features indistinguishable from acute viral hepatitis. Clinical presentation of methamphetamine hepatotoxicity ranges from mild acute hepatitis with prompt recovery to fulminant hepatic failure. The pathophysiology of this hepatotoxicity is not well elucidated. Prenatal exposure to methamphetamine has been linked to intrauterine growth retardation and variety of withdrawal symptoms. Neonatal cholestasis is rare but serious problem that indicates hepatobiliary dysfunction and has several categories of etiologies. These include infectious, metabolic, endocrine, toxic, structural, familial, and autoimmune disorders. Cholestatic hepatitis is a recognized complication of exposure to some drugs including carbamazepine and trimethoprim-sulfamethoxazole. A 35-week preterm, appropriate for gestational age, white girl was born to a 39-year-old mother who had no prenatal care. The mother's urine drug screen revealed methamphetamine. The baby passed pale meconium and her subsequent stools were hypo-pigmented. A detailed work up was done and was unremarkable except for hepatobiliary scintigraphy, with no activity noted in the small bowel on delayed imaging. An operative cholangiogram and liver biopsy were performed. The cholangiogram revealed patent bile ducts. Liver biopsy was consistent with acute viral or toxic hepatitis. Gradual drop of bilirubin was noted. With negative extensive work up for other etiology, known hepatotoxicity of methamphetamine, early onset of cholestasis that improved without specific therapy, it is strongly suspected that prenatal exposure to methamphetamine is the most likely culprit in this patient. This is the first recorded case of neonatal cholestasis related to prenatal exposure to methamphetamine. Methamphetamine is considered the fastest-growing illicit drug in United States. Hence, prenatal exposure to methamphetamine is expected to rise. Healthcare providers should become aware of the possibility of methamphetamine effect on the fetal liver. Raising awareness of the expectant mothers through the healthcare profession may reduce the risk of this condition.