Cell surface receptors play a central role in the regulation of both cellular and systemic physiology by mediating intercellular communication, facilitating protein trafficking, and regulating virtually all intracellular processes. Receptor expression is often cell specific and is determined by cellular lineage, genetics, and a variety of factors in the extracellular milieu. As receptors are generally localized on the plasma membrane and differentially expressed in certain cell types and tissues, they provide a potential target for drug delivery. However, since most receptors are integrally connected with intracellular signal transduction networks, targeting via these receptors may elicit a biological response. This review describes some established and emerging concepts regarding the structure and functions of receptors. In addition, some aspects related to the regulation and crosstalk between receptors are discussed.