Patients with cancer are living longer due to earlier diagnoses and remarkable improvements in treatments. Unfortunately, neurologic complications from chemotherapy remain a significant cause of morbidity and may play a role in limiting potential treatments. In addition, novel therapies such as small molecule tyrosine kinase inhibitors and monoclonal antibodies have also been associated with neurologic complications. Because treatments for therapy-induced neurotoxicity are limited, awareness of common neurologic complications is important to prevent permanent damage. The authors review common neurologic complications of chemotherapy and novel systemic agents in this article. This article has been updated to include neurologic complications of newer targeted agents including ipilimumab.