This perspective on Kadara et al. (beginning on p. 702 in this issue of the journal) examines the critical development of genomic and proteomic signatures of lung cancer risk, prognosis, and sensitivity to chemoprevention or chemotherapy. The novel work of Kadara et al. represents the first demonstration that a molecular signature developed in a premalignancy model (in this case, cultured normal human bronchial epithelial cells and increasingly transformed derivative cells) is clinically relevant to invasive lung cancer.