Cholestasis caused by drugs is an important differential diagnosis in patients presenting with a biochemical cholestatic pattern. The extent of serologic tests and radiological imaging depends on the clinical context. The underlying condition of the patient and detailed information on drug use, results of rechallenge, and the documented hepatotoxicity of the drug are important to establish a diagnosis of drug-induced liver injury (DILI). Most cases of cholestatic DILI are mild, but in rare cases, ductopenia and cholestatic cirrhosis can develop. Approximately 10% of patients with cholestatic jaundice caused by drugs develop liver failure.