Skeletal muscle is the most abundant component of the mature mammalian phenotype. Designed to generate contractile force and movement, skeletal muscle is crucial for organism health, function and development. One of the great interests for muscle biologists is in understanding how skeletal muscle adapts during periods of stress and stimuli, such as disease, disuse and ageing. To this end, genomic-based experimental and analytical approaches offer one of the most powerful approaches for comprehensively mapping the molecular paradigms that regulate skeletal muscle. With the power, applicability, and robustness of ‘omic’ technologies continually being developed, we are now in a position to investigate these molecular mechanisms in skeletal muscle to an unprecedented level of accuracy and precision, heralding the dawn of a new era of functional genomics in the field of muscle physiology. (Figure presented.).