The Centers for Disease Control and Prevention's Adapting Clinical Guidelines for the Digital Age initiative aims to redesign and improve guideline development, implementation, and standardization. Historically, aspects of guideline development and implementation have been siloed. This leads to long lag times for guidelines to reach patient care, unnecessary redundancy, and potential for misinterpretation, leading to inconsistencies in how the recommendations are applied. A multidisciplinary, multiorganizational holistic approach brought together experts in guideline development, informatics, communication, implementation, and evaluation to understand and identify problems in guideline development and implementation, define an ideal state with no constraints, and then design a future state that advances the process close to the ideal state. The Adapting Clinical Guidelines for the Digital Age workgroups each worked on one focus area and included experts from the other areas to help analyze the current state and develop holistic solutions for the future state. Each workgroup produced interrelated standards, processes, and tools that can be used across the continuum of guideline development and implementation.