Hepatotoxicity represents one of the most prevalent drug-induced adverse effects seen in the clinic and is a major cause of attrition of new chemical entities in development. Some adverse drug reactions are associated with metabolic activation to a chemically reactive intermediate. The hepatotoxicity associated with acetaminophen (APAP; paracetamol) and furosemide (FS) in mice is initiated by the formation of a reactive metabolite which has been well characterised. APAP hepatotoxicity is a major clinical problem, and with FS represents an important tool to investigate mechanisms of drug induced liver injury (DILI) in animal models.