Skeletal muscles are composed of several types of fibers with different contractile and metabolic properties. Genetic background and type of innervation of the fibers primarily determine these properties, but thyroid hormone (TH) is a powerful modulator of the fiber phenotype. The rates of contraction and relaxation are stimulated by TH, as are the energy consumption and heat production associated with activity. Quantitative and qualitative changes in substrate metabolism accommodate the increase in ATP turnover. Because of the total mass of skeletal muscle, these changes affect whole-body physiology. Although apparently straightforward, the phenotypic shifts induced by TH are highly complex and fiber specific. This review addresses the mechanisms by which TH may modulate fiber gene expression and discusses some of the implications of the TH-regulated changes in metabolic and contractile phenotype of skeletal muscle.