In the 15 yr since the Institute of Medicine defined clinical practice guidelines (CPG) as “systematically developed statements to assist practitioner and patient decisions about appropriate healthcare for specific clinical circumstances” (1), there has been an upsurge in their promulgation. The Agency for Healthcare Research and Quality lists more than 2000 active CPG. The factors that have driven the profusion of clinical practice guidelines are essentially the same that have driven a general increase in evidence-based decision-making and the field of outcomes research. Evidence strongly suggests that standardization of medical practice can provide cost-effective care that improves outcomes (2). Despite the seemingly compelling virtue of CPG, they are certainly not a panacea for all of the ills in health care delivery. CPG usually focus on improving the management of one particular disease, often neglecting to provide guidance on the integration of complex medical regimens for patients with multiple comorbid diseases (3,4). When CPG are linked to clinical performance measures, the result can be an increase in auditing and regulation without necessarily improving patient outcomes (5,6). Grading evidence for CPG remains complex, with multiple varying systems and approaches available (7,8). Different conclusions can arise when applying different grading systems to the same body of evidence …