By linking two scientific disciplines—immunology and morphology—immunohistochemistry has developed into an important tool in research and clinical pathology. In the last decade of the twentieth century, the efforts of histochemists led to a significant improvement in reagents and staining protocols. Milestones in this development were the heat-induced antigen demasking technique, signal amplification, and multiple immunolabeling. This chapter discusses the problems that are of particular importance in current immunohistochemical practice. Using clear and easily adaptable protocols, this chapter provides some examples of its use in both science and routine pathology.