The discovery of beta-adrenoceptors in previously unsuspected cell types is contributing to the rethinking of new drug targets. Recent developments in B-adrenoceptor pharmacology might have excited and surprised James Black, given his interest in developing drugs based on the selective manipulation of receptors to alter physiological responses. beta-adrenoceptors continue to generate surprises at molecular and pharmacological levels that often require knowledge of receptor location to interpret. In this review, we emphasize the use of fluorescent ligands as the most selective means of demonstrating receptor localization. Fluorescent ligand binding in live tissues can provide quantitative pharmacological data, under carefully controlled conditions, relevant to other signalling parameters. Consideration of the role of beta-adrenoceptors in many cell types (previously ignored) is needed to understand the actions of drugs at beta-adrenoceptors throughout the body, particularly in the lung epithelium, vascular endothelium, immune cells and other 'structural' and 'restorative' cell types.