Biopsies of suspected drug-induced liver injury pose a particular challenge to the pathologist that requires a careful and systematic approach. The initial evaluation should be as objective as possible, setting aside consideration of the medical history. Histological changes are catalogued with attention to the hepatic architecture, noting the intensity and character of inflammation, cholestasis, apoptosis and necrosis. Bile ducts, portal vessels, hepatocytes, sinusoidal lining cells and vessels are each examined for evidence of injury. The assessment culminates with the determination of the overall pattern of injury. Armed with this information, the pathologist correlates the findings with the patient’s medical and pharmacological history. Drug induced liver injury is always a diagnosis of exclusion, so the emphasis should be on identification of potential competing causes of injury. If alternate etiologies of injury can be eliminated, the histological injury pattern can be compared to the known patterns of injury of suspect medications. The histological changes can also shed light on the potential mechanism of injury in situations where the suspect agents are new and do not yet have reports of hepatotoxicity. The pathological findings, the histological differential diagnosis and expert interpretation are part of a complete biopsy assessment and provide information that is of greatest value in patient management.