There is increasing concern that patients with chronic HIV infection may be at increased risk of nonalcoholic fatty liver disease (NAFLD), which can evolve into nonalcoholic steatohepatitis (NASH) and cirrhosis. Multiple factors have been hypothesized to be necessary for the development and progression of this condition. Potential risk factors, which tend to accumulate in the HIV-positive population, include metabolic derangements, chronic inflammation, hepatitis coinfection, and treatment with certain nucleoside reverse transcriptase inhibitors (NRTIs). HIV-associated conditions such as hyperlactatemia and lipodystrophy frequently overlap with fatty liver disease. The cornerstone of management of HIV-associated fatty liver disease is currently to treat the predominant underlying condition. There is a need for more epidemiologic data to better define the role of comorbidities and drugs in the development of NAFLD. Further work is also needed to elucidate the pathogenesis and to evaluate the therapeutic effect of treating comorbidities and avoiding certain antiretroviral drugs.