Cancer of the esophagus continues to be a threat to public health. The common practice is esophagectomy for surgically resectable tumors and radiochemotherapy for locally advanced, unresectable tumors. However, local regional tumor control and overall survival of esophageal cancer patients after the standard therapies remain poor, approximately 30% of patients treated with surgery only will develop local recurrence, and 50% to 60% patients treated with radiochemotherapy only fail local regionally due to persistent disease or local recurrence. Esophagectomy after radiochemotherapy or preoperative radiochemotherapy has increased the complete surgical resection rate and local regional control without a significant survival benefit. Induction chemotherapy followed by preoperative radiochemotherapy has produced encouraging results. In addition to patient-, tumor-, and treatment-related factors, involvement of celiac axis nodes, number of positive lymph nodes after preoperative radiochemotherapy, incomplete pathologic response, high metabolic activity on positron emission tomography scan after radiochemotherapy, and incomplete surgical resection are factors associated with a poor outcome. Radiochemotherapy followed by surgery is associated with significant adverse effects, including treatment-related pneumonitis, postoperative pulmonary complications, esophagitis and pericarditis. The incidence and severity of the adverse effects are associated with chemotherapy and radiotherapy dosimetric factors. Innovative treatment strategies including physically and biologically molecular targeted therapy is needed to improve the treatment outcome of patients with esophageal cancer.