The existence of chemo brain has become almost universally accepted, although many details of the concept are controversial. Data about the different types of cognitive impairment and their duration are not always consistent in the literature. We still do not know which cytotoxic agents are responsible, which characteristics make patients vulnerableand which biologic mechanisms are involved. This chapter reviews the recent literature and provides an actualized definition of chemo brain, including recent functional imaging data and discusses its controversial aspects. Potential underlying mechanisms and their future possible clinical applications in the prevention and treatment of chemo brain are also discussed. These issues are of clinical importance given the prevalence of breast carcinoma, the increased use of chemotherapy as adjuvant therapy, the increasing use of more aggressive dosing schedules and the increasing survival rates. Better-designed future trials should lead to a better definition and understanding of chemo brain and to future therapies.