Survivors of childhood cancer are at increased risk for therapy-related morbidities and mortality. Although the demographic and clinical factors predicting the risk for long-term effects of cancer therapy are well known, the impact of genetic risk for specific late effects is less clearly defined. Here, we review the extant literature and recent research describing genetic modifiers to risk for the more common late effects of childhood cancer therapy. Results of this research support the need for clinical trials that attempt to further refine risk prediction by incorporating genetic testing into existing algorithms that are primarily based on clinical and demographic factors. Confirmation of genetic predisposition, as defined by reproducibility and prospective validation, would permit therapeutic modification and discussion of individualized survivor care plans even at initial cancer diagnosis.