Treatment of patients having malignancy near or within the spinal cord can be more challenging or limited than in patients with brain tumors. This is largely because of the near total lack of noneloquent neural tissue associated with the spinal cord and/or intimately associated peripheral nerves. The adverse effects of surgery, radiation therapy, and chemotherapy or multimodality therapy can be acute or chronic, insidious, and often permanent in nature. Because cancer therapies (particularly combination therapies) have become more effective with regard to tumor control, the potential impact of each modality on spine and peripheral nerve injury has become even more significant. Similarly, with increasing survival, the likelihood of observing long-term injury is likely to increase. Thus, the expression of acute and long-term spine and peripheral nerve injury is becoming a more important factor in the management of patients with spine malignancies. This review presents current management and investigations associated with these modality-related injuries.