The worldwide increase of AIDS, an epidemic infection in constant development has an essential and still requires potent antiretroviral chemotherapeutic agents for reducing the integer of deaths caused by HIV. Thus, there is an urgent need for new anti-HIV drug candidates with increased strength, new targets, superior pharmacokinetic properties, and compact side effects. From this viewpoint, we first review present strategies of anti-HIV drug innovation and the synthesis of heterocyclic or natural compound as anti-HIV agents for facilitating the development of more influential and successful anti-HIV agents.