AbstractCancer treatment with chemotherapy or radiotherapy causes gonadal toxicity in male patients. The endpoint of most concern for future reproductive options is the induction of prolonged azoospermia, which may or may not be reversible. The immediate effects of therapy and its reversibility are most readily observed in post‐pubertal patients, but the same antineoplastic regimens given to prepubertal males can induce permanent azoospermia. The probability of permanent azoospermia is related to the specific agents used and their doses. The most damaging are alkylating agents (particularly chlorambucil, procarbazine, cyclophosphamide, melphalan, and busulfan), cisplatin and radiation to the region of the testicles. Pediatr Blood Cancer 2009;53:261–266. © 2009 Wiley‐Liss, Inc.