The concept of a learning health system (LHS) was established nearly 20 years ago as a unifying commitment to speed the generation and use of evidence primarily by leveraging rapid advances in data and technologies, resulting in optimized care for each patient. In the ensuing decades, vanguard adopters of the LHS who have sought to move the LHS from conceptual to operational have done so in ways that fit with and reflect their organizational structure, mission, and culture-as well as their personal values and experiences. They have also extended the focus from health care to include individual and population health more broadly. This commentary describes four distinctive models that have evolved as learning health system activities have matured. Viewing this diversity as a strength, the features, commonalities, and unique differences of these models are described.