Adjuvant chemotherapy (AC) plays now a significant role in the treatment of resected non-small cell lung cancer (NSCLC) patients and has become standard in clinical practice. It took more than two decades of clinical research to show its value, but it is has been well established that its benefit translates into a 4-5% absolute increase in 5-year survival according to published meta-analysis. This improvement is obtained with two-drug, Cisplatin-based regimens (multiples choices are acceptable but vinorelbine is the drug with more reported evidence) and usually four courses are recommended. Survival increase is restricted to cases in which there is involvement of lymph nodes (both N1 and N2 levels). For N0 cases AC might be considered, with a lower level of evidence, for tumors larger than 4 cm in diameter. At the present time, molecular predictive factors and gene signatures are investigational. Patient selection is of paramount importance. Proper recovery from surgery and the absence of major comorbidities are essential features. Toxicity is significant, but manageable and transient. Neutropenia is the most relevant side effect due to the risk of febrile neutropenia. The role of timing of administration, adjuvant radiotherapy (RT) and of newer drugs under evaluation is also reviewed.