Aldosterone is the hormone responsible for salt balance in the body, so that excessive amounts can cause high blood pressure. Aldosterone has also recently been found to contribute to the development of congestive heart failure, making an understanding of the regulation of aldosterone production important to human health and disease. The primary regulator of aldosterone production is angiotensin II (AngII), which generates a number of signaling molecules that direct aldosterone-producing cells to make the hormone. Even more interesting, AngII also causes the generation of priming, a type of cellular memory, in which aldosterone-producing cells that have been exposed to AngII “remember” this pretreatment and respond to a subsequent exposure with enhanced aldosterone synthesis. Our laboratory has identified the signaling enzyme phospholipase D (PLD) as a mediator of aldosterone secretion in response to AngII. Moreover, this enzyme seems to underlie, at least in part, the AngII-elicited induction of priming. In the following review, we discuss the data supporting a role for PLD in the AngII-induced priming of aldosterone secretion, as well as a possible mechanism of action of this enzyme and the lipid second messengers it produces. We also propose that this mechanism may underlie other types of cellular memory, as occur for instance in the immune and nervous systems.