This article will discuss the role of two classes of serine/threonine protein kinases in the regulation of gene transcription in mammals. The first is AMP-activated protein kinase (AMPK), which is responsive to changes in the intracellular energy status. The second is the 'stress-activated" family of protein kinases, members of the mitogen-activated protein (MAP) kinase superfamily, whose regulation by a number of extracellular agents (including osmotic stresses, cytokines, and heat) is less well understood. Interest in these enzymes has grown in the past few years due to mounting evidence (both pharmacological and genetic) which has implicated them in the regulation of a number genes important in mammalian metabolism.