Lung cancer kills more Americans annually than the next four most frequently diagnosed malignancies combined. Single-modality therapy is the standard for most cases of limited and metastatic non-small cell lung cancer, but treatment of locally advanced disease remains controversial. Historically, radiotherapy alone was used; more recent approaches include single-agent or combination chemotherapy. The combined chemoradiotherapy approach, versus single-modality chemotherapy or irradiation, has improved on survival. Investigators have also recently shown an advantage to adding chemotherapy with or without radiotherapy to definitive surgery. Better staging systems and definitions of biologic prognostic factors may help determine the optimal therapy for locally advanced non-small cell lung cancer patients.