Named for one of Indiana's most celebrated poets, The James Whitcomb Riley Hospital for Children was founded in 1924 as Indiana's only hospital solely dedicated to the health care of children. Since its inception, Riley Hospital has grown to be the 5th largest children's hospital in the country, serving as a consultation and referral center for infants, children and adolescents throughout the state of Indiana and the Midwest. Affiliated with the Indiana University School of Medicine, Riley Hospital also serves as a teaching facility for medical students and residents.

Riley Hospital is located on the campus of the Indiana University School of Medicine on the west side of Downtown Indianapolis. Within walking distance are Wishard Memorial Hospital and the Indiana University Hospital; Riley Hospital is also connected to Methodist Hospital, approximately one mile from Riley, by a new monorail train system. The Herman B. Wells Center for Pediatric Research is located across the street from Riley and is connected by a pedestrian bridge. The research center is one of only twelve in the nation funded by the NIH as a Neonatal Clinical Research Center. The Department of Pediatrics at Indiana University has more than 150 full time faculty, in addition to all pediatric surgical subspecialties and geneticists. The department ranks in the top 20 in the country in funding from the National Institutes of Health.

Nearly 8,000 patients are admitted to Riley Hospital each year, with nearly 120,000 visits to the outpatient facilities. Riley houses the only pediatric burn center and pediatric dialysis center in the state of Indiana. The pediatric pulmonary program, the pediatric cardiology program, and the Riley Cancer Center are among the largest in the nation. Riley is also supported by the Ronald McDonald House of Indiana, one of the largest in the world. Riley Hospital is also supported by the Riley Children's Foundation, which provides financial support to the hospital through public and private donations, enabling Riley to care for all children in Indiana, regardless of their ability to pay.