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Collagen fibrils consist of a core of various collagen types associated with several non\u2010collagenous binding partners and confer tensile strength to tissues, while elastic fibers, composed of cross\u2010linked elastin on a fibrillin\u2010rich scaffold, ensure elasticity and resilience. Far from being mere degradative enzymes, proteases are key regulators of both the assembly and turnover of these networks. Metalloproteinases of the BMP1\/tolloid\u2010like, meprin and ADAMTS families orchestrate procollagen maturation, while lysyl oxidases and related enzymes drive covalent cross\u2010linking of collagen and elastin fibers, also under proteolytic control. Matrix metalloproteinases (MMPs) and cysteine cathepsins further modulate collagen structure and degradation, generating bioactive fragments used as clinical biomarkers. In parallel, ADAMTS and ADAMTS\u2010like proteases orchestrate fibrillin microfibril organization, fibulin interactions, and the topography of elastogenesis. Elastolytic proteases\u2014including cathepsins K, S, and V, as well as MMP2, MMP7, MMP9, and MMP12\u2014mediate physiological remodeling but also fuel pathological states when dysregulated, releasing elastin\u2010derived peptides that act as potent signaling matrikines. Genetic or acquired defects in these proteolytic pathways underlie diverse connective tissue diseases such as osteogenesis imperfecta, Ehlers\u2013Danlos, and acromelic dysplasias, as well as fibrosis, emphysema, and vascular aging. 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