This review describes the mechanisms of drug resistance of the most clinically relevant mycobacteria and the methods that have been used for studying drug susceptibility (pnenotype, genotype and in vivo tests) and it describes the more important resistance mechanisms to the drugs. Also, this review describes the relationship between microbiological and pharmacological data and the importance of latency -stationary phase- in mycobacteria. Current clinical guidelines on the treatment of tuberculosis (populations of Mycobacterium tuberculosis within the host, drugs and duration, importance of HIV infection in the treatment of tuberculosis, and treatment of latent tuberculosis) and other diseases caused by mycobacteria (specially associated a Mycobacterium kansasii, Mycobacterium avium complex, Mycobacterium fortuitum and Mycobacterium chelonei) are commented in view of drug resistance information, including the more commonly accepted treatments to these diseases. In addition, the impact of pharmacological studies in predicting response to therapy is reviewed. Finally, it describes the new methods of susceptibility testing and the new antituberculous drugs.