Approximately 10 years ago, the HFS-TB was developed by Gumbo et al. and first presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Since that time, the model has been refined to become more sophisticated in its utility and application, which has expanded to include the ability to influence effective dose selection in clinical settings. The HFS-TB enables a quantitative understanding of the relationship between dynamic drug concentrations, as well as dynamic populations of drug-susceptible and drug-resistant Mycobacterium tuberculosis, over time.