Pulmonary mycobacterial infections are an increasing clinical problem. The complex task of isolation and identification of the specific mycobacteria requires special stains, cultures, biochemical testing, and nucleic acid probes. Once the organism has been identified, the therapy with multiple drugs will be dictated by the type of organism and its drug susceptibility. An increasing number of patients presenting with drug-resistant tuberculosis or nontuberculous pulmonary mycobacterial infections require individualized, prolonged multi-drug regimens. The thoracic surgeon must be aware of the subtleties of mycobacterial pulmonary infections because diagnosis and failed medical treatment may require surgical intervention.