Glioblastoma is an aggressive primary tumor of the central nervous system. This review will focus on clinical developments and management of newly diagnosed disease, including a discussion about the incorporation of molecular features into the classification of glioblastoma. Such advances will continue to shape our thinking about the disease and how to best manage it. With regards to treatment, the role of surgical resection, radiotherapy, chemotherapy, and tumor-treating fields will be presented. Pivotal studies defining our current standard of care will be highlighted, as will key ongoing trials that may influence our management of glioblastoma in the near future.