Non-melanoma skin cancer (NMSC) is the most common cancer worldwide. Among the two types of NMSC, basal cell carcinoma (BCC) accounts for approximately 75% to 80% of cases and cutaneous squamous cell carcinoma (cSCC) accounts for 20% to 25% of cases. The majority of lesions are low risk and treated with simple surgical excision, which provides histopathologic information and is associated with high cure rates and acceptable cosmetic and functional outcomes. cSCCs are generally more aggressive than BCCs. NMSC commonly occurs in the sun-exposed head and neck region (80% to 90%). Approximately 5% of patients with NMSC (mainly cSCC) will have clinicopathologic features that predict for an increased risk for local and regional recurrence and, rarely, distant relapse. These features include locally advanced primary disease (stage T3-T4), regional nodal involvement, clinical perineural invasion, recurrent disease following treatment, and immunosuppression. Patients who have these features may warrant review by a multidisciplinary tumor board and might require combined modality treatment involving surgery and adjuvant radiation therapy (RT). This article focuses on our current understanding of the prognostic factors and role of adjuvant RT in high-risk NMSC of the head and neck.