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Medical schools and residency programs have always sought excellence in the areas of education, research, and clinical care. However, these pursuits are not accomplished within a vacuum—rather, they are continually and necessarily influenced by social, cultural, political, legal, and economic forces. Persistent demographic inequalities coupled with rapidly evolving biomedical research and a complex legal landscape heighten our collective awareness and emphasize the continued need to consider medicine’s social contract when selecting, educating, and developing physicians and physician–scientists.Selection—who gains access to a medical education and to a career as a physician, researcher, and/or faculty member—is as much art as science. Quantitative assessments of applicants yield valuable information but fail to convey the full story of an applicant and the paths they have taken. Human judgment and evidence-based practice remain critical parts of implementing selection processes that yield the desired outcomes. Holistic review, in promoting the use of strategically designed, evidence-driven, mission-based, diversity-aware processes, provides a conceptual and practical framework for marrying the art with the science without sacrificing the unique value that each brings.In this Commentary, the authors situate medical student selection as both responsive to and informed by broader social context, health and health care needs, educational research and evidence, and state and federal law and policy. They propose that holistic review is a strategic, mission-driven, evidence-based process that recognizes diversity as critical to excellence, offers a flexible framework for selecting future physicians, and facilitates achieving institutional mission and addressing societal needs.