Patients with MAC-PD and pre-existing lung disease are a distinct group from the more common and recently recognized group of predominantly middle- to older-aged women without pre-existing lung disease. Those with pre-existing disease are expected to have more sputum positivity and slower conversion of sputum with treatment, and they may require combined medical treatment with surgical resection for optimal results. Attention to bronchial hygiene, avoidance of unnecessary use of macrolides, and treatment of underlying esophageal and lung disease can result in marked symptomatic improvement in many cases. Appropriate consideration must be given to mycobacterial antibiotic treatment, and awareness must be maintained for other processes such as bronchogenic cancer in select groups of high-risk patients.