<p>As persons living with human immunodeficiency virus (HIV) infection are living longer, non-AIDS-related mortality continues to rise, with liver disease being one of the most common causes. This Review provides a synopsis of the current burden of liver diseases, ranging from viral hepatitis to metabolic dysfunction-associated steatotic liver disease to liver cancer, and discusses the barriers and challenges to screening and treatment as well as cofactors contributing to increasing disease burden. A brief insight is provided on the potential molecular mechanisms driving hepatic inflammation and fibrosis in persons living with HIV. Given the effect of direct-acting antivirals on hepatitis C virus infection and suppressive treatment for hepatitis B virus infection, special attention is drawn to the emergence of metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis in this population, focusing on factors related to the increasing prevalence of relevant comorbidities, the role of antiretroviral therapy, and HIV-specific factors in driving liver fibrosis progression.</p>