Although it is commonly said that the notions of sensitivity and specificity were first defined by Jacob Yerushalmy in 1947, the sensitivity and specificity of diagnostic tests have been assessed as far back as the early 1900s. These notions share a common origin with the development of serology. They were originally immunologic concepts, closely associated with the development of complement fixation reactions for syphilis. Here, the authors trace how immunologic sensitivity and specificity were transformed into diagnostic sensitivity and specificity. By relocating the origins of these concepts to the early 20th century, they highlight how these origins were bound to then-commonplace assumptions about specific infectious disease entities.