The connective tissue of tendon and skeletal muscle is a crucial structure for force transmission. A dynamic adaptive capacity of these tissues in healthy individuals is evident from reports of altered gene expression and protein levels of the fibrillar and network-forming collagens, when subjected to mechanical loading. While it appears that the fibroblast is a key player in sensing and responding to loading, the issue of how these signals are converted into changed gene expression is not fully understood. It is clear, however, that the loading-induced response involves a variety of growth factors, in particular TGF-beta-1, and matrix remodelling enzymes such as MMP-2. Furthermore, it is under hormonal influence. In skeletal muscle, the extracellular matrix demonstrates its potential for cross-talk by regulating the activity of cells with which it is in contact. Taken together, the studies highlighted in this article provide strong evidence for the highly adaptable nature of connective tissue in muscle and tendon.