Tuberculosis (TB) is a serious public health problem worldwide Tuberculosis (TB) is reported as one of the most prevailing life-threatening health problems, affecting almost one third of the population globally. It is one of a major reason of death with an imposing amplified socio-economic impact. Tuberculosis patients have infrequent endocrine and metabolic derangements, but they are important when they occur. Multiple drug regimen, poor patient compliance, and stiff administration schedule are factors that are answerable for the development of and extensive drug resistance (XDR) and multi drug resistance (MDR) instances in TB along with poor drug targeting effects. The emerging resistance strains and high transmittance rate of the disease have prompted the need for studies in advanced drug delivery, particularly nanotechnology for the management of TB. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis.