Desmoid tumors are rare, locally invasive mesenchymal tumors without metastatic potential. Their clinical behavior is heterogeneous and characteristically unpredictable; outcomes are influenced by anatomic location, proximity to vital organs, association with familial adenomatous polyposis. Surgery is the main treatment modality, but the significance of positive resection margins remains controversial since they may not increase the risk of recurrence: in this setting re-resection, adjuvant radiation or close clinical follow-up could all be appropriate options. We reviewed the current evidence for multimodality therapy of desmoids, with a focus on the importance of resection margins, and present our own algorithm for treatment.