OBJECTIVE: Drug-induced liver injury (DILI) is a global problem and can develop from exposure to prescription or over-the-counter medications as well as herbal and dietary supplements. The diagnosis of DILI is clinically challenging, and liver injury can be severe leading to liver failure, death, or liver transplantation. Patients with underlying chronic liver diseases (CLD) may be at increased risk for DILI, which is associated with factors related to drug or liver disease. METHODS: This review summarises current knowledge on the risk and outcomes of DILI in patients with CLD. RESULTS: Patients with CLD may be at an increased risk for DILI. Additionally patients with underlying CLD are at risk for more severe liver injury and worse outcomes after DILI. DISCUSSION: The risk for and poor outcomes from DILI are accentuated in patients with CLD and potentially leading to the worst-case scenario of acute-on-chronic liver failure. We highlight the key observations on DILI with a broad range of underlying liver diseases and the high-DILI risk agents implicated in those populations.