Survival rates for all stages of non-small-cell lung cancer (NSCLC) are dismal. Despite complete resection of early-stage NSCLC, many patients have recurrence at distant metastatic sites, reinforcing the need for effective systemic adjuvant therapy. Chemotherapy, and more recently, targeted therapies, have been evaluated in the adjuvant setting. Although initial trials did not suggest improved survival, a 1995 meta-analysis favored adjuvant cisplatin-based chemotherapy. The recently published International Adjuvant Lung Trial confirms this finding and suggests a new standard of care. In this paper we review data on adjuvant chemotherapy and limitations of recent clinical trials, including those with targeted therapies. We also address the most effective and least toxic regimens for adjuvant chemotherapy and the subsets of patients likely to derive the most benefit.