The erythrocyte sedimentation rate is a simple, inexpensive laboratory test that clinicians have used for decision-making for over 50 years. Despite this fact, many criticize the test because of its lack of specificity and because the concept of erythrocyte sedimentation rate as a "sickness index" seems scientifically unsound. This review discusses the physical and chemical properties that govern red blood cell sedimentation, how sedimentation is measured, and the way in which the erythrocyte sedimentation rate has previously been used to assist in the diagnosis of infectious, inflammatory, or neoplastic disease. The clinical significance, sensitivity, specificity, and predictive value of a low or elevated erythrocyte sedimentation rate are also re-evaluated.