The worldwide misuse of antimicrobials and subsequent rise of the multi-drug resistant (MDR) opportunistic intracellular pathogens have led to a paradigm shift in the established perspective of antimicrobials and bacterial-human relations. Antibiotic resistant strains of mycobacterium tuberculosis have threatened the progress in management and control of worldwide epidemic of tuberculosis. Mycobacterium tuberculosis intrinsically resists many antimicrobials, limiting the number of compounds available for treatment. Typically, conventional treatments for these diseases consist of long-term therapy with a combination of bioactive (s) that can cause side effects and contribute to low patient compliance. The escalation of antimicrobial resistance poses compelling demand for new ways of treating bacterial infections. The main objective of this chapter is to review the potential applications of nanotechnology-based drug delivery systems in combating drug resistance associated with opportunistic intracellular pathogens with special reference to tuberculosis.