1. Skeletal muscle is a complex and heterogenous tissue capable of remarkable adaptation in response to exercise training. The role of gene transcription, as an initial target to control protein synthesis, is poorly understood. 2. Mature myofibres contain several hundred nuclei, all of which maintain transcriptional competency, although the localized responsiveness of nuclei is not well known. Myofibres are capable of hypertrophy. These processes require the activation and myogenic differentiation of mononuclear satellite cells that fuse with the enlarging or repairing myofibre. 3. A single bout of exercise in human subjects is capable of activating the expression of many diverse groups of genes. 4. The impact of repeated exercise bouts, typical of exercise training, on gene expression has yet to receive systematic investigation. 5. The molecular programme elicited by resistance exercise and endurance exercise differs markedly. Muscular hypertrophy following resistance exercise is dependent on the activation of satellite cells and their subsequent myogenic maturation. Endurance exercise requires the simultaneous activation of mitochondrial and nuclear genes to enable mitochondrial biogenesis. 6. Future analysis of the regulation of genes by exercise may combine high-throughput technologies, such as gene-chips, enabling the rapid detection and analysis of changes in the expression of many thousands of genes.