During most of recorded history, the application of knowledge to the care of individual patients was founded on the experience of individual medical practitioners; when published, it basically took the form of case reports. Not until the middle of the 20th Century did randomized controlled trials (RCTs) come to be the gold standard. By the beginning of the 21st Century, however, the limitations of RCTs and their syntheses, the meta-analyses, have come to be recognized, and their applicability to the individual patient questioned and, indeed, challenged. The intense increase in our knowledge base and in accompanying technology has made possible the personalization of medicine beyond the possibilities of earlier periods. The approach of personalized medicine requires evaluation of four parameters: the individual patient's intrinsic susceptibility, intrinsic morbidity, extrinsic susceptibility, and extrinsic morbidity. The characteristics of the disease agent--how much (duration) and how virulent--also must be factored in. These individualized data define the appropriate intervention: high susceptibility and/or morbidity or low susceptibility and/or morbidity and the aggregate of the intrinsic and extrinsic risk factors are cofactored in medical decision making.