Adenocarcinoma of the small intestine is rare in comparison with other gastrointestinal malignancies but its incidence is rising. It often presents at an advanced stage due to the non-specific symptomatology. More recent advances in small intestinal visualisation including video capsule endoscopy and double balloon enteroscopy may facilitate diagnosis in patients with suspected small intestinal neoplasia. At present aggressive surgical resection provides the best chance of cure of small intestinal adenocarcinoma. Despite apparent curative resection the long-term outlook remains poor. The role of adjuvant chemotherapy is not well defined due to the rarity of the disease and lack of randomised controlled trials; however, there appears to be a survival benefit in advanced disease with the use of oxaliplatin and 5-fluorouracil. We reviewed the clinical aspects of this aggressive condition focusing on the pathological associations, available diagnostic modalities and current management options. Three cases are included to illustrate the review.