The advent of highly active antiretroviral (ARV) agents has led to striking reduction in plasma viral load, opportunistic infection and mortality from AIDS. Unfortunately most of these drugs have poor physiochemical, metabolism or transport properties that result in poor or variable absorption and side effects, which are often related to the accumulation of the drug at inappropriate sites. Various classes of antiretroviral agents are available, though monotherapy in HIV positive individuals can develop resistance more quickly as compared to combinational therapy or fixed dose combination or highly active antiretroviral therapy. The currently available ARV drugs mostly oral formulations, which are associated with several disadvantages and inconveniences to the HIV patients. The delivery of drugs via oral route suffers from significant first-pass effect, variation of absorption and degradation in the gastrointestinal, erratic bioavailability, limited duration of drug action, metabolism/elimination and transport barriers reducing the effect of anti-HIV drugs reaching the target site. Also half-life of several ARV drugs is short, which requires frequent administration of doses leads to poor patient compliance. Therefore, the usage of novel drug delivery systems is a logical approach to circumvent these problems and effectively treat the HIV infection. Various novel drug delivery techniques were tried or on trial for ARV drugs. Among the recent approaches of novel drug delivery system for anti-HIV drugs, controlled/sustained and targeted/intracellular drug delivery are the important ones. In this review the need for novel drug delivery, advantages, and recent development in drug delivery system of antiretroviral drugs were discussed, which may useful for further research in future.