Adenocarcinoma of the small intestine is a rare malignancy with limited data available to guide therapeutic decisions. Delays in diagnosis are frequent and the majority of patients will present with advanced-stage disease and either lymph node involvement or distant metastatic disease. Furthermore, the role of adjuvant therapy in patients who undergo curative resection is unclear. Recent retrospective and prospective studies have helped to clarify the optimal chemotherapy approach for advanced small bowel adenocarcinoma. The combination of capecitabine and oxaliplatin is highly active, with a median overall survival of 15 months in patients with metastatic disease. Further clinical studies in this rare tumor type are needed. This article reviews the clinical features and evaluation of patients with small bowel adenocarcinoma and focuses on recent advances in management.