Clinical practice guidelines are fundamental to support knowledge and decision making of healthcare professionals in many disciplines. They can contribute to reducing undesirable practice variation, educating patients, and monitoring care. However, the burden increases if the number and size of guidelines continues to increase and as more side effects occur due to injudicious use, both in the professional and policy setting. Restricting the scope and finding the right balance between completeness and conciseness are major challenges for guideline developers and stakeholders. Ongoing innovation projects are working on improving accessibility, updating, and applicability in multimorbidity through optimal use of digital technologies. As long as healthcare professionals are in the lead in guideline development and involved in policy making, doctors can continue to rely on guidelines, if used correctly for the right care.