The hospital-based histology laboratory experienced several changes in the 1960s and 1970s when cryostats, enclosed tissue processors, plastic cassettes, and disposable knives were introduced. Other than the emergence of immunohistochemistry in the 1980s, few major changes have occurred. But now, driven by costs, higher expectations, and a desire for faster turnaround times, these laboratories are on the brink of changes that will involve additional new duties for the pathologist and the histotechnologist. New techniques, some already in use in some hospitals, will involve flow cytometry, fluorescence in situ hybridization (FISH), DNA and genetics studies, proteomics, telepathology, and digital imaging. New antibodies in immunohistochemistry and new biomarkers will assist in diagnoses. Accrediting agencies will raise their standards to meet the new challenges. Although no one really knows what will happen in the future, this article reviews the new changes that will likely occur in hospital histology, based on present predictions and technology.