Objectives: To discuss recent and current initiatives to increase enrollment of adolescents and young adult (AYA) cancer patients onto National Cancer Institute-funded clinical trials to improve outcomes. Data Sources: Peer-reviewed publications, websites of professional organizations. Conclusion: Despite many challenges facing AYAs, recent studies illustrate that AYA-focused cancer clinical trials can be successfully developed and conducted. Development of the National Cancer Institute National Clinical Trials Network and related AYA-focused initiatives create new opportunities to expand clinical trials that serve AYAs. Implications for Nursing Practice: Nurses can influence AYA outcomes by leveraging their roles as educators and collaborators to increase participation in cancer clinical trials.