Antimicrobial therapy of infections caused by M. tuberculosis is a challenge due to poor response to therapy and recurrent infections. Under in vitro conditions, antibiotics effectively kill M. tuberculosis within the first two weeks. However, an extended treatment time of 6-9 months is required to eradicate M. tuberculosis infection, mainly due to the intracellular survival of this pathogen and poor penetration of the antibiotics into the intracellular compartment of the host cells. Recent advances in the field of drug delivery have led to the use of different antibiotic incorporated nano- and micro- formulations such as liposomes, polymeric particles, mesoporous silica particles and particulate suspensions for targeted drug delivery applications into the intracellular compartment of the macrophages. The drug incorporated nano- and micro-particles are prone to be easily internalized, which leads to preferential delivery of the drugs into the tissues and organs of interest. Other advantages of these nano- and micro-particles over the free drugs are their comparatively higher stability and bioavailability. This review highlights the current strategies and challenges in treatment, the different antibiotics available, their modes of action, generation and mechanism of drug resistance and recent advances in the intracellular drug delivery using nanoparticles for the treatment of tuberculosis.