Driven by reports of unmet clinical needs and lack of survival improvement, programs for adolescents and young adults (AYAs) with cancer have become increasingly common across the United States during the past 10 years. Programs generally originate from existing pediatric or adult hospitals, serve all or a subset of patients between 15 and 39 years of age at the time of cancer diagnosis, and aim to work collaboratively with other branches of their institution to deliver superior care for AYAs. Until recently, programs responded to local needs and evolved without an established framework for growth. Over the past several years, organizations including NCCN have published guidelines for AYA cancer care and for the development of clinical AYA programs. This article reviews these publications, describes the growth and development of 2 nationally recognized AYA centers—Seattle Children’s Hospital and Moffitt Cancer Center—and offers practical suggestions to assist developing AYA programs. AYA oncology is entering a new era of increasing public recognition and nationally coordinated growth, as evidenced by the recent establishment of the Change it Back’s Centers of Excellence Program that codifies criteria for excellence in AYA cancer care. AYA programs have the potential to improve care for a vital and underserved patient population, stimulate collaborative research, and enhance relationships with patients, the local community, referring physicians, and donors.