High-grade astrocytomas include the most common adult central nervous system (CNS) tumor, glioblastoma multiforme, and anaplastic astrocytoma--a highly aggressive cancer with short median survival despite maximal multimodality therapy. Diagnosis is by clinical and radiographic findings confirmed by histopathology. Standard-of-care therapy includes surgical resection, radiotherapy, and temozolomide. Nearly all patients who have high-grade astrocytomas develop tumor recurrence or progression after this multimodality treatment. Two treatment challenges are molecular/genetic heterogeneity of tumors and limited CNS tumor delivery. It is probable that targeted therapies will be most effective in combination with one another or with cytotoxic therapies. This article discusses diagnosis and current treatment of high-grade astrocytomas.