Purpose of review Small cell lung cancer is a chemosensitive malignancy, yet long-term survival remains elusive for the majority of patients. Here, we report on progress in evaluating novel targeted therapies for the treatment of this disease. Recent findings Interferons, matrix metalloproteinase inhibitors, thalidomide bevacizumab, ZD6474, imatinib, gefitinib, oblimersen and aplidine have all entered clinical trial in patients with small cell lung cancer. Immunotherapy approaches targeting cell surface antigens such as CD-56 (BB10901) and GD3 ganglioside are also being evaluated. Interferons, matrix metalloproteinase inhibitors, imatinib and gefitinib have failed to demonstrate efficacy for this disease. Preliminary data for thalidomide are promising and so results from trial of other antiangiogenics such as bevacizumab and ZD6474 are awaited with interest. Summary Although the promise of targeted therapy has yet to be realized in patients with small cell lung cancer, the number of agents available for evaluation provides new optimism that progress will be made over the next decades.