Tuberculosis (TB) is one of the most devastating diseases primarily due to several decades of neglect and presents a global health threat of escalating proportions. TB is second leading infectious cause of mortality today behind only HIV/AIDS. The impetus for developing new structural classes of anti-TB drugs comes from the emergence of multi drug-resistant (MDR) strains to commonly used drugs, substantially longer durations of therapy that are needed because of resistance, and the resurgence of disease in immuno-compromised patients. Recent years have witnessed emergence of many new structural classes of anti-TB agents, which have exhibited promising activities against drug-sensitive and drug-resistant strains of the causative organism Mycobacterium tuberculosis. These analogues ideally should decrease the overall duration of therapy with improved efficacy, and exhibit mechanisms of action different from those of existing drugs to counter the resistant strains of M. tuberculosis. This review provides a comprehensive literature compilation on advances in the new structural classes of anti-TB analogues reported during the past eight years. Our discussion and observations are concentrated on chemotherapeutic potential of thirty-eight new structural classes of anti- TB agents that includes:- acetamides, 5-arylidene-2-thiohydantoins, benzoxazoles and benzothiazoles, benzoic acid hydrazones, benzoxazines, carbohydrates, chalcones, coumarins, deazapteridines, imidazoles, indoloquinazolinones, isothiosemicarbazones, mycobactins, 1,8-naphthyridines, phenazines, diaryl ethers, hydroxamic acids, nitrofurans, N-substituted amino acids, purines, pyridines, pyrimidines and thymidines, pyrroles, phenothiazines, pyrazoles, pyrrolidine carboxamides, quinolines, quinoxalines, isoxazoles, diarylmethanes, taxanes, thioureas, terpenes, thiadiazine thiones, thiolactomycins, adenosines, toludines, and triazoles.