A wide spectrum of Gram-positive/Gram-negative bacteria has been found resistant to a wide spectrum of antibiotics in the United States of America during the past decade. Drug-resistant tuberculosis is not yet a major threat in North/South America, Europe, and the Middle East. However, the migration of populations in times of drought, famine, and hostilities may increase the global reach of this ancient pathogen. Given an increased spread from China and India to African countries, drug-resistant Mycobacterium tuberculosis has become an emerging topic of concern for Europe and North America. Due to the dangers associated with the spread of pathogens among different populations, the World Health Organization continues to expand healthcare advisories for therapeutic approaches for both stationary and migrating populations. As much of the literature focuses on endemic to pandemic viruses, we remain concerned that other treatable communicable diseases may be ignored. One such disease is multidrug-resistant tuberculosis. We focus on molecular mechanisms that this pathogen relies upon for the development of multidrug resistance via gene mutation and the evolutionary development of new enzyme and calcium channels.