Formerly the treatment of gastrointestinal cancers was exclusively surgical. Though the results were improved by increased radicality, the real progress was achieved by the introduction of multimodal therapy, particularly by the neoadjuvant concept. The basic prerequisite for neoadjuvant treatment is precise staging and risk assessment. According to staging patients can be divided into three categories: (1) Early cancers, confined to the mucosal and submucosal layers, are approached with primary surgery. (2) Systemically metastasized tumors receive merely palliative treatment. (3) Locally advanced cancers are treated by neoadjuvant therapy. Due to neoadjuvant treatment the tumor can be downsized (or downstaged) in some patients. These are the responders benefiting from the therapy, because of the increased RO-resection rate, decreased recurrence rate and improved survival. The non-responders, by contrast have poor prognosis. Neoadjuvant treatment considerably improved the chance for cure for patients with gastrointestinal cancers, thus this method became an evidence based treatment for locally advanced gastrointestinal cancers.