Small intestine adenocarcinoma is a rare tumor of the gastrointestinal tract, but its incidence is increasing. Small intestine adenocarcinoma has similar molecular characteristics as colorectal carcinoma, but it has also different features. There are different chemotherapeutic agents and regimens that can be used in the the management of adenocarcinoma of the small intestine. Each agent has its distinct mechanism of action and pharmacokinetic properties. The use of these agents and regimens depend primarily on the stage of the disease, patient condition and molecular status of the tumor. New targeted therapies can be developed in the future due to the molecular characterization of this tumor and its pathogenesis.