The nature of healthcare delivery has changed dramatically during the 20+ years since clinical practice guidelines first became a central focus of efforts to improve healthcare quality and outcomes. Continued development of new clinical and service delivery technologies, dramatic shifts in fiscal and regulatory environments, and continued changes in delivery system structure and organisation are among the key drivers of evolution in healthcare delivery practices. This presentation highlights key features of this evolution and derives important implications for clinical practice guideline implementation. Key implications include the need to (1) embed guidelines in broader efforts to reorganise and redesign care delivery, including team-based multidisciplinary care, (2) expand efforts to integrate guideline recommendations in health information technology applications targeting consumers and other stakeholders, in addition to clinicians, and (3) better coordinate and integrate guidelines within clinical policies, quality and performance monitoring schemes and technical assistance and quality improvement initiatives. Additional trends in healthcare technologies and delivery practices have implications for guideline development processes and guideline attributes, in addition to guideline implementation. These include growing interest in personalised medicine and patient-centred care, the emergence of “big data” and associated opportunities to develop new forms of evidence-based guidance for clinical decisions, and continued developments in clinical research methods such as observational designs for comparative effectiveness research, “N of 1” trials and others. The presentation will touch briefly on these developments as well, and discuss their implications for the future of clinical practice guidelines as a foundation for evidence-based clinical decision making and quality improvement.