Background and Objectives: Diagnostic and therapeutic approaches to mediastinal tumors have changed over the past three decades. We reviewed our recent experience with these tumors and assessed the role of a multidisciplinary treatment approach. Methods: A retrospective review of 124 patients with primary mediastinal tumors over a 25-year period. Results: Median age was 35 years. Symptoms were present in 86 of 124 (69%) patients. One hundred and eleven of 124 (90%) tumors were malignant. Distant metastases were present at diagnosis in 14 of 124 (11%) patients. The most common tumor was thymoma (38/124, 31%), followed by germ-cell tumor (29/124, 23%), lymphoma (24/124, 19%), and neurogenic tumors (15/124, 12%). Seventy-four of 124 (60%) patients underwent resection, 88 (71%) received chemotherapy, and 97 (78%) received radiation therapy. Tumor recurrence occurred in 52% (47/91) of patients who initially had a complete resection or response to treatment. Median time to recurrence was 10 months. Overall median survival was 44 months. Metastatic disease at presentation (P β«Χ‘β¬ 0.02) and tumor recurrence (P β«Χ‘β¬ 0.00001) were the only significant independent predictors of survival on multivariate analysis. Conclusions: Malignant primary mediastinal tumors often require multimodality treatment. Despite improvements in survival with multimodality treatment, death from recurrent disease remains a problem.