Cancer therapy can cause several neurotoxic syndromes that are associated with distinct findings on cranial imaging. With the use of more aggressive and combined treatment modalities in oncology and prolonged overall patient survival, neurotoxicity has been reported with increasing frequency in patients with brain cancer and malignancies outside the nervous system. Both cranial irradiation and chemotherapy can be harmful to the nervous system, and be associated with acute and chronic nervous system toxicity. Here we discuss features and imaging characteristics of common neurotoxic syndromes, such as cerebrovascular complications, reversible leukoencephalopathy syndrome, progressive white matter injury, and diffuse brain atrophy. Neurologist and oncologists need to be familiar with the pattern, time course, and evolution of both acute and long-term neurologic complications of cancer therapy. Identification of causative agents and appropriate distinction between treatment-related toxicity and tumor-associated complications are critical steps to improve treatment monitoring and overall patient care.