The 5'-AMP-activated protein kinase (AMPK) functions as an intracellular fuel sensor that affects metabolism and gene expression. AMPK is activated in skeletal muscle in response to exercise and is therefore believed to be an important signalling molecule in regulating adaptation of skeletal muscle to exercise training. This review first focuses on mechanisms regulating AMPK activity during muscle contraction. We then discuss the role of AMPK in regulating expression of genes encoding various enzymes in muscle in the basal state and in relation to exercise training. Although decreased AMPK activity in muscle causes reduced protein expression of mitochondrial enzymes in the basal state, AMPK does not appear to be indispensable for exercise-training induced increase in mitochondrial enzyme expression.