A nihilistic approach to the treatment of patients with medically inoperable, early stage non-small cell lung cancer (NSCLC) is not warranted. Despite the frequency of comorbid medical illness in patients with medically inoperable NSCLC, lung cancer progression is the major cause of morbidity and death. Although expectations for cure are reduced compared to good-risk patients (eg, adequate pulmonary reserve), modest long-term survival rates of patients have been reported, after definitive therapy. A comparison of radiotherapy and limited resection is difficult because of the lack of randomized data and the selection bias inherent in retrospective reports. For example, patients treated with surgery have peripheral lesions, undergoing rigorous staging compared to patients treated with radiotherapy. In a multidisciplinary thoracic program, patients are counseled on the options of sublobar resection and conformal radiotherapy. The efficacy of adjuvant radiotherapy, after limited resection, in reducing local recurrence in patients with medically inoperable NSCLC is unclear. However, adjuvant radiotherapy may be considered if a postoperative target volume can be defined, particularly if resection margins are narrow. Considering the benefit of chemoradiotherapy for patients with locally advanced disease, combination therapy is administered to patients with good performance status and large (eg, > 4 cm) primary lesions, although combined therapy may increase the potential for pulmonary toxicity in patients with baseline pulmonary dysfunction. Prospective data are becoming available to define the value of treatment alternatives for patients with medically inoperable NSCLC. The Cancer and Leukemia Group B completed a phase II study of thoracoscopic wedge resection and postoperative radiotherapy, whereas a phase I trial of dose-intensive accelerated conformal radiotherapy is ongoing. Trials involving systemic therapy for patients with medically inoperable NSCLC should be developed.