Immunohistochemistry (IHC) provides valuable information on expression of proteins within tissues at a cellular and subcellular level. Recent developments in the practice of IHC now make it possible to contemplate using this technique as a high-throughput expression profiling system. Advances have been made in creation and use of tissue microarrays, in automated IHC and in image capture/analysis. Each of these technologies are reviewed and issues surrounding their use considered. The success of high-throughput IHC is also dependent on both generation and screening of appropriate antibodies. Antibody-related issues which are likely to affect the success of high-throughput IHC, such as specificity, sensitivity, fixation choice, etc., are also considered.