OBJECTIVE: The management of head and neck squamous cell carcinoma (HNSCC) has substantially changed over the past two centuries. This review explores the historical progression of HNSCC management focusing on the multidisciplinary treatment paradigm. DATA SOURCES: This review synthesizes data from historical and current clinical trials, books, scientific reports, public documents, and other written material relevant to HNSCC management. REVIEW METHODS: Historical review. RESULTS: Although surgery was initially the only treatment available, radiation, chemotherapy, and immunotherapy have expanded the treatment landscape for HNSCC. Despite continuous evolution, modern treatment of HNSCC remains rooted in a multidisciplinary, personalized approach. This review highlights the clinical pioneers who established the standards of care and the landmark trials that progressed it. The optimal timing, application, and extent of different treatments, including the role of neoadjuvant therapy, remain under study. Immunotherapy has improved outcomes for recurrent/metastatic mucosal HNSCC and cutaneous malignancies, although its role in the curative management of mucosal HNSCC is still materializing. CONCLUSIONS: Surgery and radiotherapy have made continued gains in reducing morbidity and treatment sequala. Platinum-based chemotherapy remains the mainstay of systemic therapy for HNSCC, but there has been accelerated growth in the application of immunotherapy and targeted therapy. Comprehensive head and neck cancer care depends on multidisciplinary management, usually requiring multiple treatment modalities while individualizing both the therapies and treatment goals. Additional phase III trials are needed to further define the optimal treatments for HNSCC.