An increasing incidence of deaths due to tuberculosis and the known drawbacks of the current existing drugs including the emergence of multi drug-resistant strains have led to a renewed interest in the discovery of new anti-tubercular agents with novel modes of actions. The recent researches focused on natural products have shown a useful way to obtain a potentially rich source of drug candidates, where alkaloids have been found more effective. The present review focuses on current epidemiology of tuberculosis, synergy of the disease with HIV, current therapy, available molecular targets and, highlights why natural products especially alkaloids are so important. The review summarizes alkaloids found active against mycobacteria from the mid-1980s to late 2008 with special attention on the study of structure-activity relationship (SAR).