In the time since its discovery, phosducin's functions have been intensively studied both in vivo and in vitro. Phosducin's most important biochemical feature in in vitro studies is its binding to heterotrimeric G protein βγ-subunits. Data on phosducin's in vivo relevance, however, have only recently been published but expand the range of biological actions, as shown both in animal models as well as in human studies. This review gives an overview of different aspects of phosducin biology ranging from structure, phylogeny of phosducin family members, posttranscriptional modification, biochemical features, localization and levels of expression to its physiological functions. Special emphasis will be placed on phosducin's function in the regulation of blood pressure. In the second part of this article, findings concerning cardiovascular regulation and their clinical relevance will be discussed on the basis of recently published data from gene-targeted mouse models and human genetic studies.