The purpose of this review article is to examine the various studies that have evaluated microspheres for delivery of antimycobacterial drugs. Some of the studies strictly involve the development and evaluation of microspheres for use in antimycobacterial drug delivery, whereas others actually use drug-loaded microspheres to treat mycobacterial infections in cell lines and small animals. Although there is a potential to use microspheres to treat a variety of mycobacterial infections, it appears that most of the studies so far have focused on the etiological agent of tuberculosis, Mycobacterium tuberculosis. As a result, the infectious studies presented here all entail the treatment of that mycobacterial agent. This review will address the following aspects that are important if microspheres are to be considered an acceptable therapeutic tool: 1) in vitro release characteristics, 2) delivery, release and efficacy in macrophages, 3) effectiveness in infected small animal models, 4) safe and combined use with other antimycobacterial agents, and 5) reduced toxicity. It is hoped that once all of these parameters are evaluated, a conclusion regarding the benefit of microsphere technology in the treatment of mycobacterial diseases can be reached.