Diffuse gliomas in adults continue to have a dismal prognosis with the current standard therapeutic methods, including maximal surgical resection, radiation, and chemotherapy. The pathogenesis of adult glioma is complex, involving the loss of function of tumor suppressor genes and activation of oncogenes, which are involved in a network of interconnected signaling pathways. Through activation of these pathways, characteristics of malignant gliomas, including uncontrolled proliferation and growth, invasion, and angiogenesis, are driven. Evolving therapeutic approaches are focused on specifically targeting these genetic lesions. This content gives an overview of the current knowledge about the pathogenesis of adult diffuse gliomas, emphasizing new targeted treatment approaches.