Dramatic advances in the understanding of the molecular mechanisms of membrane receptor activation for several prototypic members of different families of receptors have taken place during the past 2-3 years. The new structures of receptor fragments or full-length receptors in different conformations have been reviewed previously in light of the large bodies of available structure-function data. However, in this article, we will compare, among different receptor families, the emerging paradigms for conformational changes during signaling. Recent advances in the understanding of membrane-protein folding suggest that these paradigms are closely related to those that describe the folding and structural stability of membrane proteins. These relate in particular to long-range interactions not only within but also between soluble or membrane-embedded parts of proteins.