Lung cancer is the most common cancer in the world. In the majority of cases, a tumor will have already become disseminated at the time of diagnosis, and extensive efforts to improve diagnosis and therapy have had no major success so far. Lung cancer gene expression profiling provides novel diagnostic and prognostic markers and a basis for targeted therapies involving small-molecule and antibody-based approaches. To enhance further research and to translate knowledge gained at the molecular level into novel therapeutic concepts, this review summarizes gene expression analyses of lung cancer performed at the RNA level using suppression subtractive hybridization, serial analysis of gene expression and cDNA and oligonucleotide microarrays, and discusses major findings.