HIV infection results in profound alterations of immunologic function that render the patient severely immunocompromised, and susceptible to malignancies and opportunistic infections. Three AIDS-defining malignancies include Kaposi's sarcoma (KS), non-Hodgkin's lymphoma (NHL) and invasive cervical cancer. In AIDS patients, KS is often aggressive and multifocal, with visceral involvement and widespread cutaneous and nodal spread; NHL is always high grade and often widely disseminated at the time of diagnosis with frequent involvement of extranodal sites; cervical cancer is invasive and has greater likelihood of progression and metastasis. Although there are very sparse systemic data available in the literature, limited studies has shown that FDG PET-CT is a valuable imaging technique in the diagnosis, staging, restaging and monitoring therapeutic response in these malignancies. In addition, a unique application of FDG PET/CT is the differentiation of cerebral lesions between lymphoma and toxoplasmosis in AIDS patients, which cannot be reliably achieved with either CT or MRI. HIV-associated opportunistic infections may involve different pathogens and multiple tissues, organs or systems. Some preliminary observations have revealed a promising role of FDG PET-CT in the diagnosis and identification of these infections such as tuberculosis, fever of unknown origin, pneumocystis pneumonia and candidiasis. However, it should be stressed that FDG PET-CT alone has no role in identifying the pathology of abnormalities. FDG PET-CT, at best, can localize the sites of abnormalities and impact on patient's management in clinical decision making.