HIV-TB co-infection especially involving MDR-TB poses a huge threat to global human population. The major therapeutic challenges involved are high pill burden, overlapping toxicity and drug-drug interactions resulting in nonadherence and poor outcome. In this scenario, the use of single class of drugs for both HIV and TB is an interesting prospect. Therefore drugs that are effective against both the diseases are need of the hour. In this book, we meticulously discuss about alpha-pyrone based compounds, a six-membered oxo-derivative of pyran that holds a promising dual-purpose key in HIV-TB drug discovery. Predominantly, alpha-pyrone based scaffolds act as a vital source of anti-HIV agents that have already acclaimed clinical place as Tipranavir, a second-generation HIV non-peptidic protease inhibitor. Interestingly, research over the years has witnessed the multi-target potency of these scaffolds against Mycobacterium tuberculosis.