Almost a decade has passed since the first paper describing the isolation and maintenance of precision-cut liver slices produced using a mechanical tissue slicer was published (1). Although tissue slices of various organs have been employed as an in vitro system for several decades, the lack of reproducibility within the slices and the relatively limited viability of the tissue preparations has prevented a widespread acceptance of the technique. The production of an automated slicer, capable of reproducibly producing relatively thin slices of tissue, as well as the development of a dynamic organ culture system, overcame several of these obstacles. Since that time, significant advances in the methods to produce and culture tissue slices have been made, as well as the application of the technique to several other organs, including kidney, lung and heart. This review will i) summarize the historical use of tissue slices prior to the development of the precision-cut tissue slice system; ii) briefly analyze current methods to produce precision-cut liver, kidney, lung and heart slices; and iii) discuss the applications of this powerful in vitro system to the disciplines of pharmacology and toxicology.