Skeletal muscle is a highly adaptable and plastic organ that responds to a single acute exercise bout by inducing the expression of genes involved in numerous functions, such as oxidative metabolism, protection against oxidative stress or improvement of the contractile apparatus. Several epigenetic mechanisms are mediators of contraction-induced gene expression, notably histone modification and changes in DNA methylation on exercise-responsive genes. These transient changes suggest that epigenetic mechanisms are not restricted to early stages of human development, but are broad dynamic controllers of genomic plasticity in response to environmental factors.