Chordomas are malignant tumors of the axial skeleton, characterized by their locally invasive and slow but aggressive growth. These neoplasms are presumed to be derived from notochordal remnants with a molecular alteration preceding their malignant transformation. As these tumors are most frequently observed on the skull base and sacrum, patients suffering from a chordoma present with debilitating neurological disease, and have an overall 5-year survival rate of 65%. Surgical resection with adjuvant radiotherapy is the first-choice treatment modality in these patients, since chordomas are resistant to conventional chemotherapy. Even so, management of chordomas can be challenging, as chordoma patients often present with recurrent disease. Recent advances in the understanding of the molecular events that contribute to the development of chordomas are promising; the most novel finding being the identification of brachyury in the disease process. Here we present an overview of the current paradigms and summarize relevant research findings.