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This chapter reviews pediatric cancer therapy and its consequences on fertility. Chemotherapy can cause infertility, premature ovarian failure, menstrual irregularity and delayed puberty. The effects of chemotherapy on ovarian function are both agent and dose-dependent, and this effect may be additive to that resulting from abdominopelvic radiotherapy. Testicular dysfunction is among the most common long-term side effect of chemotherapy in men. The germinal epithelium is very susceptible to injury by cytotoxic drugs secondary to its high mitotic rate. Reduction in the dose or use of alkylating agents and abdominopelvic radiotherapy is the most effective means of preserving ovarian function and promoting positive reproductive outcomes in pediatric cancer survivors. Sperm cryopreservation after masturbation is the most established and effective method of fertility preservation in males. Oncologists have a responsibility to inform parents and age-appropriate patients about the likelihood that their cancer treatment may permanently affect their fertility.