With the widespread adoption of multimodality treatment, 5-year survival of children diagnosed with cancer has improved dramatically in the past several decades from approximately 60% in 1970 to greater than 85% currently. As a result, there are an estimated nearly half a million long-term survivors of childhood cancer living in the United States today. However, survivors have, on average, significantly greater serious medical and psychosocial late effects compared with the general population. In this review, we will discuss the current epidemiology of childhood cancer survivorship, including new methods to estimate the burden of late effects and genetic susceptibility toward late effects. We will also review the development of surveillance guidelines for childhood cancer survivors and early toxicity signals from novel agents now being tested and used increasingly to treat pediatric and adult cancers. We conclude with an overview of current models of survivorship care and areas for future research.