In this article, the American Cancer Society provides estimates of the number of new cancer cases and deaths for children and adolescents in the United States and summarizes the most recent and comprehensive data on cancer incidence, mortality, and survival from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries (which are reported in detail for the first time here and include high-quality data from 45 states and the District of Columbia, covering 90% of the US population). In 2014, an estimated 15,780 new cases of cancer will be diagnosed and 1960 deaths from cancer will occur among children and adolescents aged birth to 19 years. The annual incidence rate of cancer in children and adolescents is 186.6 per 1 million children aged birth to 19 years. Approximately 1 in 285 children will be diagnosed with cancer before age 20 years, and approximately 1 in 530 young adults between the ages of 20 and 39 years is a childhood cancer survivor. It is therefore likely that most pediatric and primary care practices will be involved in the diagnosis, treatment, and follow-up of young patients and survivors. In addition to cancer statistics, this article will provide an overview of risk factors, symptoms, treatment, and long-term and late effects for common pediatric cancers. CA Cancer J Clin 2014;64:83–103. © 2014 American Cancer Society.