Exciting news regarding lung cancer was presented at the American Society of Clinical Oncology (ASCO) 2005 Annual Meeting held in Orlando, FL. Last but not least among the big killers, after breast cancer and colorectal cancer, non-small cell lung cancer (NSCLC) can now benefit from the addition of a molecularly targeted agent to standard first-line chemotherapy. The Eastern Cooperative Oncology Group 4599 phase III trial showed superior survival in patients with advanced nonsquamous NSCLC when the angiogenesis inhibitor bevacizumab was added to standard first-line chemotherapy with carboplatin and paclitaxel, compared with the same chemotherapy alone. Careful patient selection is mandatory to avoid fatal bleeding following bevacizumab administration. The role of surgery in the multimodality treatment of stage III NSCLC was further defined by the North American Intergroup 0139 trial and the European Organization for the Research and Treatment of Cancer Lung Cancer group 08941 trial. The final results of the Adjuvant Navelbine International Trialist Association trial add further support to adjuvant platinum-based chemotherapy following radical surgery in early-stage NSCLC. Interesting studies further addressed the correlation between molecular tumor profiling and clinical outcome with molecularly targeted agents in NSCLC, in particular gefitinib and erlotinib. Still, the Southwest Oncology Group 0023 randomized trial of maintenance gefitinib after definitive chemoradiation in unresectable NSCLC failed to demonstrate an advantage for maintenance gefitinib over placebo. Unfortunately, no striking results have been reported for small cell lung cancer and pleural malignant mesothelioma. The results of the studies in this report are updated with the data presented at the 2005 ASCO Annual Meeting.