The extracellular matrix (ECM) is basically defined as the structure that provides physical support to the cells and determines the boundaries of the tissues. This structure, which provides the supportive environment for the cells, can be seen in more detail, and we can see the existence of an environment for the differentiation of cells, morphology, proliferation and migration. This environment also serves as a repository with the growth factors which it contains. The main biomolecules found in the intercellular matrix can be defined as proteoglycans, glycosaminoglycans and collagen. Some of these structures serve as cell surface receptors as well as the presence of intercellular matrix. This situation is very important for signal transmission when it is considered as cell-matrix interaction. In this regard, a relationship is established between intracellular and extracellular environment. The proper placement of cells and their resumption in parallel with the tissue development process are closely related to well-organized ECM structure. We see the importance of this relationship especially in the musculoskeletal system diseases, which have clinical consequences, and in the synthesis process of scaffold structures based on tissue engineering applications. Especially in the areas where natural biomaterials are used, the ECM organization gains importance. It is also apparent that the ECM organization is forefront in three-dimensional cell culture studies. These versatile features of the ECM structure seen in the work are related to the organization of the ECM in physiological conditions. Understanding of the organization of ECM in both diseases and normal physiological conditions is very important. In this review, the biochemical and physical basis properties of the ECM structure and related ECM diseases will be revealed. Also, in recent years, approaches to cell-ECM interaction, which have been carried out under the heading of particularly regenerative medicine will be explained.