Molecularly targeted therapies that are more tumor specific in their efficacy, with associated fewer toxicities, are currently being developed. Specific biomarkers that may predict response or resistance to a particular agent are being sought. Several classes of compounds now target specific steps in cellular proliferation and apoptosis. These include epidermal growth factor receptor (EGFR) inhibitors, vascular endothelial cell targeting agents, matrix metalloproteinase inhibitors, farnesyltransferase inhibitors, retinoids, proteosome inhibitors, and raf/MAPkinase (mitogen-activated protein kinase) inhibitors. Many of these agents, such as bortezomib, have demonstrated promise in the fields of non-small cell lung cancer (NSCLC). However, a cautionary perspective must be maintained because agents such as bexarotene, which showed promise in early studies, have proved disappointing in randomized trials. As the number of therapeutic agents increases in NSCLC, there will be greater emphasis on the selection of an appropriate patient population in which to give specific, targeted therapies.