Desmosomes are a complex assembly of protein molecules that mediate adhesion between adjacent cells. Desmosome composition is well established and spatial relationships between components have been identified. Intercellular cell-cell adhesion is created by the interaction of extracellular domains of desmosomal cadherins, namely, desmocollins and desmogleins. High-resolution methods have provided insight into the structural interactions between cadherins. However, there is a lack of understanding about the architecture of the intact desmosomes and the physical principles behind their adhesive strength are unclear. Electron Tomography (ET) studies have offered three-dimensional visual data of desmosomal cadherin associations at molecular resolution. This review discusses the merits of two cadherin association models represented using ET. We discuss the possible role of sample preparation on the structural differences seen between models and the possibility of adaptive changes in the structure as a direct consequence of mechanical stress and stratification.