It is undeniable that the introduction of chemotherapeutic drugs has significantly increased the survival of cancer patients. In recent years, new drugs are being developed for cancer treatment, but the use of classical chemotherapeutic agents is still essential. Unfortunately, most treatments, including current antitumor drugs and newer treatments, come with important adverse effects. Therefore, characterization and treatment of the adverse effects and sequelae associated with chemotherapy is an urgent clinical need. Drugs used to combat cancer inhibit the proliferation of tumor cells and induce apoptosis or other forms of cell death. But these mechanisms are also responsible for the development of undesirable side effects as other types of cells may be affected, including neurons, which are not fast-dividing cells. Thus, chemotherapy may induce neurotoxicity. The blood-brain barrier is responsible for the protection of the central nervous system, but it is still vulnerable to antitumoral drugs. Central side effects of chemotherapy are diverse and include encephalopathy, headache, seizures, cerebellar syndromes, visual loss, myelopathy, cerebrovascular complications, and confusional states. In addition, chemotherapy has been correlated with mild deficits of memory and cognition, known as chemotherapy-induced cognitive impairment, “chemobrain,” or “chemofog.” These central toxicities could be the result from direct damage to neural tissues as well as from systemic causes. This chapter will review and compile the main symptoms of central neurotoxicity described in patients treated with conventional chemotherapy. To facilitate understanding, the main antitumoral drug classes have been summarized according to their mechanism of action.