There is an underlying feeling in the oncology community that chemotherapy has reached a therapeutic glass ceiling in non-small cell lung cancer (NSCLC) and that we will never attain the acceptable survival rates that are just beyond our reach. Multiple clinical trials have tested doublets, triplets and sequential chemotherapy in what is often regarded as a futile attempt to break through this ceiling. Recent large randomized trials have not demonstrated that any of these combinations is superior to any of the others. Nevertheless, the analysis of DNA or RNA from patients can permit us to assess genes that may be specific targets of certain cytotoxic agents and others that may be markers of multidrug resistance. With this in mind, the Spanish Lung Cancer Group has designed a trial to test the involvement of various genes in resistance to gemcitabine and cisplatin.