The present review is a highly biased personal perspective on some of the research carried out over the last 50 years documenting the phenomena and the mechanisms of skeletal muscle tissue malleability. I will take a historical approach and follow some of the threads that have spurred my curiosity and have guided my research over my research career. This review is not exhaustive nor is it balanced. It represents my personal interests and some of the crucial findings that shaped my research agenda. I was lucky to conduct this research with many inventive collaborators that have done the major share of the actual research work. I have also been fortunate to have two outstanding mentors, E.R. Weibel and C.R. Taylor, who supported me throughout my research with advice guidance and, at least initially, with the necessary financial support. They have fostered a comprehensive approach and have taught me to combine functional and structural research to arrive at an integral view of system performance. When the appropriate molecular tools became available in the late 90ies, these helped start to unravel the mechanisms underlying the structural and functional plasticity of muscle documented previously. The insight that skeletal muscle tissue, when actively used is a major determinant of human physical well-being and health, continues to boost mechanistic research in muscle plasticity in the future.<\/p>\n\n