© 2016 Sadhana Nittur Holla et al. With the introduction of antiretroviral therapy, there is a dramatic decrease in the morbidity and mortality related to human immunodeficiency virus (HIV) infections. Due to varying degree of immunosuppression, patients are prone to various number of infections in their lifetime. Respiratory system, central nervous system, gastrointestinal tract and the skin are the most susceptible for opportunistic infections. Timely management of these microbial infections followed by chemoprophylaxis is essential as per the guidelines for the management of opportunistic infections in HIV. The development of drug toxicities and drug resistance in managing patients with HIV has always remained a clinical challenge. Consideration is given to the numerous pharmacokinetic interactions between drugs used to treat and prevent opportunistic infections and antiretroviral drugs, along with complications like immune reconstitution inflammatory syndrome. Clinicians must be aware about optimal strategies present for diagnosis, prevention and treatment of opportunistic infections in order to improve health and provide high quality of care for the patients.