Treatment for testicular cancer has dramatically improved during the last 15 years. Much of this success has come about because of improved staging and operative techniques but, most importantly, through the introduction of successful systemic chemotherapy. Nonetheless, relevant issues still remain to be addressed in regard to the optimal therapy for patients with germ cell neoplasms. Included in these issues is delineating the most effective but minimally morbid treatment for patients with early-stage and low-volume metastatic disease while continuing to create innovative treatment approaches for poor-risk patients with metastatic disease. The unique association of primary mediastinal germ cell neoplasms with the development of non-germ cell cancers and Klinefelter's syndrome may provide some early clues for the determination of factors controlling differentiation. These observations issue a challenge to both clinical and preclinical researchers involved in the study of this neoplasm.