Gastric cancer represents a major global health problem. Approximately half of patients are diagnosed with early stage disease and surgical resection is potentially curative. The addition of combination chemotherapy, with or without radiotherapy, to surgery has been shown to improve outcomes. In metastatic disease, combination chemotherapy in the form of 2- or 3-drug regimens has been used. The aim of this chapter is to summarize currently approved systemic treatment options for gastric cancer and to highlight several promising treatments currently under investigation.