Recently, there has been a firmer understanding of the relevant signaling pathways critical for lung cancer growth, leading to the development of novel, targeted therapies. The discovery of the EGFR and ALK pathways in lung cancer and the subsequent development of drugs that target these pathways, erlotinib and crizotinib respectively, has yielded unprecedented survival times in stage IV non-squamous, non small cell lung cancer. Unfortunately, only 25 to 30% of patients harbor these mutations, and platinum based chemotherapy remains the cornerstone of treatment for the 60-70% of patients with stage IV disease without identifiable targets. In attempts to improve outcome, a large need remains to develop novel, effective agents to combine with platinum therapy that possess a favorable toxicity profile at a reasonable cost.