Drug-induced liver injury (DILI) is an uncommon, but potentially fatal, cause of liver disease that is associated with prescription medications, OTC drugs, and herbal and dietary supplements (HDS). DILI has two types: intrinsic and idiosyncratic. Patient, environmental, and drug-related factors may play a role in the pathogenesis of DILI. In the United States, antibiotics and antiepileptic drugs are the most common drug classes associated with DILI, but HDS are on the rise as a cause. Management of DILI involves the removal of the offending agent and the use of N-acetylcysteine for acetaminophen-induced liver injury. Outcomes vary depending on the drug used and type of liver injury sustained. Pharmacists can play an essential role in the evaluation of DILI, especially in patients taking multiple medications and supplements.