Paraffin section immunohistochemistry (IHC) is widely used in diagnostic surgical pathology. Today, it is difficult to imagine the practice of surgical pathology without IHC. The availability of automated immunostainers with reagent rental contracts makes this technology commonplace. One potential danger is that many laboratories are now offering immunostains without significant prior knowledge or experience in IHC. As part of its mission, the Cell Markers Committee of the College of American Pathologists offers this manuscript as a basic guide to introducing new antibodies in the clinical IHC laboratory. Issues relating to regulatory developments, antibody selection, staining optimization, and test validation are addressed.