The available data suggest that selected patients with tuberculosis and MAC fail to respond to therapy because they malabsorb their medications. In particular, patients with AIDS and known gastrointestinal diseases have problems absorbing these drugs. In addition, because MDR-TB and MAC are so difficult to treat, TDM with the antimycobacterial drugs offers the clinician a chance to ensure that the patient achieves serum concentrations above the MIC of the pathogen. TDM has become the standard of practice at the National Jewish Center for Immunology and Respiratory Medicine. By combining specific and sensitive assays, carefully collected samples, and clinical expertise, we are able to control and optimize antimycobacterial drug therapy. We continue to refine our approach with ongoing pharmacokinetic and pharmacodynamic research, including the development of population pharmacokinetic models. We hope that these efforts will provide insight into the nature of current therapeutic problems. We also hope they will help us improve the clinical outcomes of our patients.