Despite advances in the management of non-small-cell lung cancer (NSCLC), including the introduction of targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors, improvements in survival are marginal and the overall prognosis for patients remains poor. Tailoring therapy to the individual patient is a promising approach for selecting the most appropriate therapeutic regimens to maximize efficacy and minimize toxicity. The identification of predictive biomarkers that can guide treatment decisions is an important step for individualized therapy and in ultimately improving patient outcomes. Genomic and proteomic studies provide a means for the molecular profiling of tumor tissue from patients with NSCLC, and allow tailoring of therapy whereby the most appropriate treatment is administered to each individual patient. Although there are still significant challenges to implementing genomic and proteomic testing in clinical practice, the rapid development of newer technologies provides hope for overcoming these barriers.