We review the changes in incidences of HIV-related opportunistic infections and the safety of discontinuation of primary and secondary prophylaxis for HIV-related opportunistic infections in patients achieving immune restoration after the introduction of highly active antiretroviral therapy (HAART). HIV-related opportunistic infections continue to occur in patients who are newly diagnosed with HIV infection, those in the early course of HAART or non-adherent to HIV care and HAART, and those in whom non-HIV-related infections have emerged as a significant cause of morbidity and mortality in the post-HAART era. Clinical studies of patients with tuberculosis and HIV co-infection are reviewed to provide appropriate regimen combinations of rifamycins and antiretrovirals, which have varying degrees of drug-drug interactions that have posed challenges in the management of tuberculosis as well as HIV infection.