With recent advances in the Human Genome Project and progress in microarray and gene chip technology, an explosion of genomic information is becoming available. One of the major ways to understand this vast amount of data is by bestowing topological information to help us identify the functional relevance of specific genes and to explain the pathogenesis of disease processes.In situhybridization is a technique that will further our understanding of the function of genes within normal tissue along with the pathogenesis of a disease process within abnormal cells. This chapter provides an overview ofin situhybridization, followed by general principles and protocols.