A growing body of evidence indicates that many cellular metabolic pathways are catalyzed not by free-oating “soluble” enzymes, but via one or more membrane-associated multienzyme complexes. is type of macromolecular organization has important implications for the overall eciency, speci-city, and regulation of metabolic pathways. An ever-increasing number of biochemical and genetic studies on primary and secondary metabolism have laid a solid foundation for this model, providing compelling evidence in favor of the so-called channeling of intermediates between enzyme active sites and co-localization of enzymes inside of a cell. Information from these studies oers new insights into the structuring of biosynthetic pathways within cells, which should lead to more eective means for engineering the production of valuable metabolites with medical and industrial importance. To gain an appreciation for how such complexes may have arisen, one need look no further than “under the hood” of any living cell.