Operable non-small cell lung cancer (NSCLC) has been traditionally managed with surgical resection, often followed by adjuvant chemotherapy with or without radiotherapy. However, disease recurrence still occurs approximately 50% of the time. Most recently, (neo) adjuvant/perioperative systemic therapy has evolved to include checkpoint inhibitor therapy and targeted therapies that have proved successful in advanced disease settings. We provide a comprehensive review of the trials investigating neoadjuvant, adjuvant, and perioperative systemic therapies in resectable lung cancer, including a discussion on surrogate survival endpoints. We review the management of N2 disease, the utility of circulating tumor DNA (ctDNA) in determining the risk and benefit from systemic therapy in operable NSCLC, as well as future directions of investigation.