Lung cancer is the leading cause of cancer-related mortality worldwide. Despite adequate resection, more than half of patients die of recurrent disease, usually at distant sites. Adjuvant systemic chemotherapy is mainly used to eradicate micrometastatic disease. Since the seminal 1995 meta-analysis from earlier studies showed a trend toward improved survival with the use of cisplatin-based adjuvant chemotherapy, several randomized prospective adjuvant trials have addressed this question and eventually established the role for platinum-based adjuvant chemotherapy in patients with stage II or IIIA non-small cell lung cancer who have undergone complete resection. The role of adjuvant chemotherapy in patients with stage I disease remains controversial. Although no clinical or molecular predictors of recurrent disease after surgical resection are reliable, encouraging preliminary data on gene expression studies suggest that identifying, and perhaps treating, only patients at high risk for relapse might be possible in the near future. Furthermore, molecular predictors of resistance may guide the selection of chemotherapy in this setting.