Survival outcomes of patients with stage IIIA non–small cell lung cancer (NSCLC) with mediastinal lymph node involvement (N2 disease) have been poor when treated with surgery alone. Numerous studies have investigated induction chemotherapy, radiation, and chemoradiation to attempt to improve outcome in this high-risk population. The appropriate application and sequence of these treatments is still the subject of ongoing study. Surgical resection appears to have the greatest benefit in patients who have decreased mediastinal involvement following induction therapy, although the type of surgical resection (pneumonectomy or lesser resection) impacts morbidity and mortality risks after induction therapy. Molecularly targeted agents are also being studied as a potential induction therapy for use in the treatment of stage IIIA disease.