As the HIV population continues to live longer as a result of antiretroviral therapy, liver-related mortality has become one of the leading causes of non-AIDS related death in this patient population. The liver possesses a remarkable regenerative capacity but undergoes complex biological changes in response to aging and inflammation that result in decreased cellular regeneration and a tipping of the scales towards fibrogenesis. Patients with HIV infection have serological evidence of ongoing inflammation, with elevations in some biomarkers persisting despite adequate virologic control. In addition, HIV-co-infected patients have markers of advanced age on liver biopsy and increased prevalence of fibrosis as compared to an age-matched HCV mono-infected cohort. In this review, we will discuss the biology of aging, age-related changes in the liver, and the relevant mechanisms by which HIV causes inflammation in the context of accelerated aging, fibrosis of the liver, and other viral co-infection.