We aimed to summarize the recent reflections and collaborative initiatives pertaining to the definition of more appropriate eligibility criteria in cancer clinical trials. There is an intrinsic tension between two opposite purposes when it comes to defining eligibility criteria: on the one hand, participants must be protected, and on the other, the study population must be defined as accurately as possible. However, stringent eligibility criteria jeopardize the feasibility of trials, and, consequently, the generalizability of trial results. Therefore, interdisciplinary working groups under the auspices of the American Society of Clinical Oncology and Friends of Cancer Research propose to adapt/relax some of the classical eligibility criteria. In-depth reflection of the existing eligibility criteria, and implementation of recent recommendations are needed.