To establish the effect of three frequently used chemotherapeutic agents in childhood cancer on the skeleton, growing male Wistar rats were studied. Treatment with doxorubicin, methotrexate, and cisplatin reduces the proximal tibial growth plate shear strength because of a decreased surface area and maximum shear stress. After treatment the bone fracture risk of the tibia and femur is increased because of decreased bending resistance. Doxorubicin and cisplatin reduce the maximum shear stress of the proximal tibial growth plate, none of the chemotherapeutic agents inhibit bone mineralization. These effects are caused by treatment-induced malnutrition and the accompanying weight reduction and a direct effect of the chemotherapeutic agents on the skeleton. The current study confirmed the importance of preventing malnutrition during chemotherapeutic treatment in view of possible skeletal complications. During followup of children treated with chemotherapy, attention should be given to signs and symptoms suggestive of such complications.