Two of the most recent hypotheses concerning metabolism and its regulation are examined. First, the theory of distributive regulatory control of metabolic pathways is considered in light of experimental evidence concerning the lack of change in flux of a pathway when individual enzymes are either increased or decreased. In addition, it is known that when flux through pathways is either increased or decreased, one finds that the amount of all the enzymes of that path increase or decrease simultaneously. Second, the hypothesis of the existence of metabolons, complexes of sequential metabolic enzymes, is examined using the Krebs TCA cycle pathway as an example. The evidence from in vitro studies with pure enzymes to in vitro metabolic studies with yeast mutants is reviewed and evaluated. Unsolved problems concerning these hypotheses which still exist are considered.