It is now firmly established that calcium is a key component of cellular adhesiveness, as shown from live tissues and cultured cells dissociating whenever exposed to a calcium-depleted environment (1). Cadherins are Ca²⁺-dependent cell-adhesion molecules that bind homotypically to identical cadherin molecules on opposing cells (2). The homotypic adhesion and Ca²⁺-binding activities reside in the extracellular region of cadherins, whereas the intracellular domain, together with adapter proteins such as α-, β-, and γ-catenins, is responsible for linking cadherin to cytoskeletal actin filaments. The coordinated intercellular and intracellular protein-protein interactions are crucial for the formation of tissue structure and the proper physiological functioning of tissues (3). Recent reviews have compiled the findings of several structural studies showing the intricate partnership between calcium binding and protein-protein interactions in cadherins (4,5). In this chapter, we will describe a variety of techniques that have been employed to study the function and structure of cadherin molecules. Because there is an excellent review of the protocols for the investigation of cadherin cellular functions (6), we will focus on the molecular and structural studies of this family of Ca²⁺-binding proteins. A brief description of a cell aggregation assays and its inhibition has also been provided.