For many years, the treatment options for patients with early-stage non-small cell lung cancer (NSCLC) were limited to surgery, with or without chemotherapy. When chemotherapy was used, a platinum-based doublet regimen has been the long-standing standard adjuvant treatment for resected patients with stage II-III disease. Adjuvant chemotherapy results in a benefit of disease-free survival (DFS) and overall survival (OS) in early-stage NSCLC with an absolute survival benefit of 4-5% compared to observation or best supportive care. In recent years, however, early-stage NSCLC has been entering the era of precision medicine. Recent trials have been testing the efficacy both of driver mutation-specific tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) (Figure 1). For oncogene-addicted disease, clinical trials mostly focused on Epidermal Growth Factor Receptor mutations (EGFRm) and Anaplastic Lymphoma Kinase (ALK) rearrangements. In the immunotherapy trials, many pharmacological agents have been tested in the adjuvant as well as neoadjuvant setting.1 In this review, we aim to report on the already available literature data with targeted agents and immunotherapy in early-stage NSCLC, focusing on the most practice-changing results and new perspectives.