Genomic technology continues to advance, and data derived from non-small-cell lung cancer (NSCLC) tumor specimens in conjunction with clinical information are accumulating at an exponential rate. Application of this information to clinical practice for the treatment of patients with NSCLC lags behind the promise of individualized patient management based on genomic medicine. Testing treatment decisions based on genomic information in cancer clinical trials is only now being addressed. How best to incorporate the myriad of potentially available molecular diagnostics into treatment algorithms is not yet clear. Many hurdles and much work remain for the development of true, individualized treatment strategies for NSCLC based on molecular staging. Here we review some of the successes, frustrations and obstacles that exist to further progress in the field.