Glycogen metabolism in the liver is subject to complex regulations in which substrates or hormones may interact in different ways according to the nutritional conditions. Activation of glycogen synthesis strongly depends on the availability of glucose, gluconeognic substrates and amino acids. These factors act mainly by a direct or indirect activation of the synthase phosphatase. On the other hand, cAMP or Ca(2+)-dependent glycogenolytic agents cause glycogen degradation by the mean of specific protein kinases which may inactivate the glycogen synthase or activate the glycogen phosphorylase. The active form of glycogen phosphorylase is a potent allosteric inhibitor of the synthase phosphatase. Insulin increases glycogen synthesis by counteracting the action of glycogenolytic hormones and by enhancing the glucose induced activation of glycogen synthase. The respective importance of these different regulations is discussed in this article.