Highly active antiretroviral therapy (HAART) has effectively decreased the incidence of opportunistic infections (OIs), and thereby reduced research efforts to find alternative treatments to prevent or treat OIs. However, research on treating OIs is still needed. For instance, It is suggested that people who are co-infected with HIV and hepatitis C virus (HCV) should not use protease inhibitors (PIs), because both PIs and HCV significantly strain the liver, and that could increase the risk of liver disease. On the positive side, a study of co-infected people found favorable results in treating HCV with Interferon-alfa, and recently a more effective combination was found with Interferon-alfa plus Ribavirin. Mycobacterium avium complex (MAC) has been successfully treated with Clarithromycin and Ethambutol, but resistance to Clarithromycin can develop. A recent study on MAC added Rifabutin to the treatment which prevented the development of resistant MAC. Suggestions are also provided for how to effectively treat cryptococcal meningitis and chronic diarrhea. The discontinuation of maintenance therapy of OIs is discussed, and recommendations are given on who may be able to discontinue maintenance therapy. Pharmaceutical companies are encouraged to continue researching, developing, and marketing affordable and accessible therapies to combat opportunistic infections.