Lung cancer has the highest incidence and mortality among cancers of both men and women. Treatment strategies for non-small-cell lung cancer, the most common form of lung cancer, continue to evolve, most recently with the positive trial results for EGF receptor (EGFR) tyrosine kinase inhibitors in the first-line setting in molecularly targeted populations. Despite these promising findings, EGFR tyrosine kinase inhibitors remain costly, and it is therefore important to assess the value of erlotinib therapy across the full spectrum of use. This is an up-to-date review of the clinical and economic impact of erlotinib for advanced non-small-cell lung cancer. Overall, the studies found that erlotinib, compared with available agents, provides slightly improved outcomes with variability in the incremental costs depending on the health system and patient characteristics. Additional studies are warranted exploring the cost-effectiveness of erlotinib as a first-line agent as well as the clinical and economic impact of EGFR mutation testing strategies versus usual care.