The functional properties of skeletal muscle tissue are essentially determined by the spatial arrangement of its constituent elements. The contractile function resides in the alignment of actin and myosin filaments together with their associated proteins as procured through the developmental process. However, muscle tissue is also endowed with an extraordinary phenotypic plasticity, allowing adult muscle tissue to respond in specific ways to changing demands imposed by the environment of by lifestyle. It has been shown in humans and animals that specific exercise training interventions can lead to massive changes in muscle strength or endurance over time periods of a few weeks. These functional gains are the consequence of well characterized muscle structural modifications. Molecular tools enable us now to study the mechanisms by which changes in functional demand lead to the observed structural modifications. During exercise muscle cells are subjected to mechanical, metabolic, neuronal and metabolic signals which are transduced over multiple partly parallel pathways to the muscle genome. Exercise activates multiple signaling cascades, the characteristic of the stress leading to a specific response of the network of signaling pathways. Signaling ultimately results in the activation of structure genes or in the case of strength training in translational activation. Repeated exercise sessions lead to concerted accretions of mRNAs which upon translation result in a stepwise increase of proteins of relevant functional entities. On the structural level the protein accretion manifests itself for instance as an increase in mitochondrial and capillary volume upon endurance training and myofibrils and associated proteins upon strength training. We have shown that a single exercise stimulus carries a molecular signature which is typical both for the type of stimulus (i.e. endurance vs. strength) as well as the actual condition of muscle tissue (i.e. untrained vs. trained). It therefore seems feasible to use molecular tools to judge the properties of an exercise stimulus earlier and at a much finer level than is possible with conventional functional or structural techniques which require weeks of exercise before a training response can be detected reliably. The current molecular techniques begin to reveal a very detailed picture of the modulatory events involved in muscle malleability. The ultimate challenge that molecular exercise scientists is facing is to extract the biologically relevant information from the sheer mass of data generated by available technology and to integrate this information into models of system physiologic relevance.