Despite considerable interest and success in oncology drug development, the minority of patients with cancer diagnoses enroll in clinical trials. Multiple obstacles account for this low enrollment rate. An improvement in patient participation in clinical trials could increase patient access to novel and potentially promising agents, provide faster trial results, and, with implementation of rational eligibility criteria, allow for a better understanding of the drug's safety and efficacy in a heterogeneous population. We present barriers and potential solutions to maximize patient participation, including a review of the ASCO and Friends of Cancer Research (FoCR) Modernizing Eligibility Criteria Project, U.S. Food and Drug Administration (FDA) regulatory considerations, an industry perspective, and a patient perspective.