For the last thirty years, ongoing efforts have revolutionized the antiretroviral therapy, which changed human immunodeficiency virus (HIV) infections from terrifying lethal diseases to chronic conditions. However, many challenges, like emergence of drug resistance, limited the scope of activity of currently existing anti-HIV agents. Quite often severe side effects and lifelong dependency are the major concerns of present era. All these issues have compelled the scientists to reconsider and refine the current therapies and also contemplate the pivotal priorities for the developments of novel therapeutic paradigms. In response to this global concern, medicinal chemists and pharmaceutical scientists have put in solid efforts to search for or develop novel, more effective, safer, and affordable antiretroviral agents for the treatment of HIV infections. The exploration and utilization of natural sources has always been an attractive research area in this regard. In the search of the most suitable and potent anti-HIV agents, researchers have explored the anti-HIV activity of different classes of compounds originating from plants, marine organisms, and microorganisms. This review will highlight the recent notable developments for the discovery of antiretroviral agents. Furthermore, this review also highlights the better in-depth insights of existing HIV cures and preventive strategies.