Clinical practice guidelines are available for many disorders, from the common cold to colon cancer. According to the Institute of Medicine, such guidelines are primarily intended to assist in physician and patient decision making. Guidelines are also meant to eliminate unnecessary and unjustified variations in practice, but their effectiveness in that regard is debatable. Naturally, clinical guidelines cannot eradicate variations because an enormous number of variables—for example, local circumstances and comorbid conditions—affect clinical decisions. Guidelines can consider variations in clinical settings, resources, and other variables, but cannot always adjust for the combination of resources that may be available to a physician. In addition, it would be unwise, even if it were possible, to provide completely uniform care because some variations, such as those that result from an individual physician's professional judgment, are acceptable. In fact, David Wennberg, MD, MPH, director of the division of health services research at the Maine Medical Center in Portland and a senior research associate at Maine Medical Assessment Foundation in Manchester, believes that physicians should welcome variations that arise from the choices of well-informed patients. However, given that some variation will and should exist, can guidelines produce clinically meaningful reductions in unnecessary and inappropriate variations in care?