From decades’ tuberculosis (TB) affecting individual and a huge number of people die every year. It causes ill-health among millions of individuals each year and ranks as the second leading cause of death from an infectious disease worldwide. The number of TB deaths has been unacceptably increased to a large extent and most cases are preventable if people get in time access to health care for a diagnosis and the right treatment. Multi-drug resistance is the fact that in TB patients are growing rapidly and difficult to treat. Treatment of MDR-TB is more complicated and longer than treatment of TB with no resistance. With advancements in the therapy of TB, now ideal treatments have been developed and many combination therapies are well recommended for MDR. The development of MDR-TB can be caused by a treatment that is inadequate, given the drug susceptibility pattern of the MTB strain. Few cohort studies provided information on treatment regimens and drug resistance profiles before treatment and at failure or recurrence or genotyping information at failure or recurrence. To monitor the development of acquired drug resistance, we suggest that given sufficient resources are available, TB treatment cohort studies or surveillance systems measure both the drug resistance profile and genotype information before starting treatment and at failure or recurrence. The emergence of MDR-TB and XDR-TB, the need for new TB drug regimens and rapid DST is intuiting globally. In future, more research with a focus on MDR and TB is required to avoid and counteract its associated complications.