Cell-cell adhesion is essential for life in multicellular organisms. One of the prominent adhesive structures acting as stabilizing element in tissues is the desmosome. In addition to providing cohesion strength to tissues subjected to high mechanical stress, it has been recently recognized that desmosomes are also essential for tissue morphogenesis and differentiation. The crucial role of the desmosome in cell physiology is mirrored by the large number of diseases occurring when the function of one or more of its constituents is impaired. Hence, major efforts have been made over the last 20 years to understand the mechanisms underlying the pathobiology of intercellular adhesion, with a hope of developing new diagnostic and therapeutic tools; this, in turn, has allowed gaining more insights into the basic science of desmosome structure and function. These concepts will be briefly presented here and developed in detail in the upcoming cell adhesion series "Desmosomes in physiology and disease", launched on the occasion of the 150th anniversary of the discovery of the desmosome in 1864.