The progression of tuberculosis from a latent, subclinical infection to active disease that culminates in the transmission of infectious bacilli is determined locally at the level of the granuloma. This progression takes place even in the face of a robust immune response that, although it contains infection, is unable to eliminate the bacterium. The factors or environmental conditions that influence this progression remain to be determined. Recent advances have indicated that pathogen-induced dysregulation of host lipid synthesis and sequestration serves a critical role in this transition. The foamy macrophage seems to be a key participant in both sustaining persistent bacteria and contributing to the tissue pathology that leads to cavitation and the release of infectious bacilli.