While lung cancer remains a very challenging cancer to treat, new treatments that capitalize on advances in our understanding of cancer biology are providing both patients and physicians with a reason for cautious optimism. Because cancer is a highly varied disease, one of the primary treatment challenges is in selecting patients who are most likely to benefit from new therapies. Researchers are now focusing on identifying biological markers, such as genetic signatures, that could indicate which tumors are most vulnerable to angiogenesis inhibitors and other targeted agents. It is likely that a more personalized approach to treatment using biological markers and combinations of therapies will provide better results in the future.