Andrographolide is a diterpene lactone and the main constituent of the traditional Chinese and Indian medicinal herb, Andrographis paniculata. Known primarily for its usefulness as a tonic and as a treatment of common viral infections, A. paniculata was suggested as a way to control HIV-1 infections in developing nations. When tested under laboratory conditions, andrographolide affects several facets of HIV-1 infection. These include (1) inhibition of HIV-1 cell-to-cell transmission, (2) inhibition of viral replication in peripheral blood mononuclear cells (PBMCs), and (3) inhibition of CD4+ T-cell death. An open-label, phase I clinical trial in 13 HIV-1-positive patients indicated that the patients displayed increased CD4+ T-cell counts after 6 weeks of andrographolide administration. At the molecular level, andrographolide acts as a kinase inhibitor and down-regulates the expression of the cell cycle-related enzymes cyclin B and cyclin-dependent kinase 1 (CDK-1) in either cancer cells or HIV-1 infected cells. By combining andrographolide with natural compounds that target other molecular sites necessary for viral reproduction, the prospect of formulating a safe and cost-effective “natural cocktail” to control HIV-1 infections is promising. Such attributes project a possible role for andrographolide in the future management of HIV/ AIDS. Since AIDS is becoming less life-threatening, the search for cost-effective medicines that can improve health and enhance the quality of life (QOL) is becoming increasingly important.