Cancer is a chief burden of disease all over the world and is perceived as a terrifying and uncurable illness that implies death. Chemotherapy is one of the most common therapeutic approaches in the treatment of cancers. The effectiveness of chemotherapeutic agents has led to a great elevation in survival rates of patients with different types of cancer. Chemobrain is a group of symptoms showing reversible or irreversible cognitive decline, which a subset of adult, non-CNS cancer patients complain as a direct effect of chemotherapy. Several studies were conducted to investigate the possible chemotherapeutic agents that may precipitate chemobrain and their possible underlying pathways and mechanisms of action. In this review, we were interested in providing an insight into chemobrain, the possible mechanistic pathways of chemobrain-inducing chemotherapeutic drugs, the possible neuroprotective agents, diagnostic methods, the possible management methods, and the possible neuroprotective agent . The data of this review were based on review articles, books, and original articles obtained from PubMed, Google Scholar, and Elsevier.