Neurologic dysfunction is a well-recognized adverse effect of cancer therapeutics. The most common manifestations include peripheral neuropathy and encephalopathy. Often, symptoms resolve or improve upon removal of the offending agent; therefore, it is essential that clinicians recognize the symptoms and signs of injury. Occasionally, symptoms persist or develop after discontinuation of medication and may culminate in disability and diminished quality of life. As our understanding of neurotoxicity improves, medications with less potential for injury may be developed. In addition, potential antidotes to prevent or reverse injury may emerge. This review focuses on the clinical features, mechanisms, and possible therapeutics of the neurotoxicity of chemotherapy. In particular, oxaliplatin, thalidomide, methotrexate, ifosfamide, cytarabine, amifostine, acetyl-L-carnitine, methylene blue, cytokines, and neurotrophins are discussed.