Extracellular matrix is a very complex assemblage of specialized molecules including collagen, elastin, proteoglycans, and attachment glycoproteins such as fibronectin and laminin. Collagen is an unusual protein because it requires multiple processing steps both within and outside the cell beginning with transcription and refinement of its messenger RNA, translation of the mature mRNA, extensive post‐translational modifications, and further alterations in the extracellular compartments. If errors are made at any one of the multiple steps in this complex pathway, a defective molecule will be formed that could result in connective tissue abnormalities. Similarly, alterations in other components of the extracellular matrix can also result in clinical pathologies. Some of these clinical phenotypes have been classified as Ehlers‐Danlos syndrome, Marfan syndrome, osteogenesis imperfecta, and epidermolysis bullosa. This article reviews these various connective tissue disorders, describes the underlying biochemical defects, and describes their impact on tissue repair.