The role of clinical practice guidelines has changed dramatically the past 50 years. Both beneficial, as also having some disadvantageous effects. Considering the international developments, such as a growing body of evidence and evolving methodologies, some limits might be in reach or already been reached. The solution thereof is part nationally and part internationally. Internationally because of new methodologies and technologies, such as use of artificial intelligence, and nationally in a more coherent approach. Coherent not only in medical disciplines, but also in policies of government, regulators, and health insurers. This calls for a renewed, integral and an all-encompassing vision.