The role of radiotherapy in treating local and regional disease in patients with clinically localized Merkel cell carcinoma remains controversial. Given the lack of randomized evidence and patient and treatment heterogeneity in published retrospective series, sound clinical judgment is required to assess individual patient risk factors. Although many single-institution series have shown that adjuvant radiation to the primary tumor site decreases the risk for local and regional failure, evidence is emerging that there is a cohort of patients at relatively low risk for local recurrence after wide local excision alone. Node dissection, radiotherapy, and combined modality treatment may all play a role in managing occult or clinically evident nodal disease, depending on the anatomic location of draining lymphatics and the extent of microscopic or macroscopic disease. For select patients, primary radiotherapy is a reasonable option with a low risk for local or regional recurrence.