Cancer in the neonate is a rare event, constituting only 0.2% of all childhood malignancies. Depsite unique therapeutic challenges posed by patients in this age group, the malignancies occurring in the neonate are often responsive to the same multimodality treatment approach used in older children, and long-term survival can often be achieved. Chemotherapy is a key component of treatment. The pharmacology of these chemotherapeutic agents in the neonate parallels developmental changes in the liver, kidney, gut, and fluid compartments. These developmental changes must be considered in the design of chemotherapeutic schedules and in the selection of drug dosages for the neonate. The factors known to be important in neonatal drug distribution and metabolism are discussed and recommendations are made for appropriate modification of chemotherapy programs based on these considerations.