Phospholipase D activity has been extensively implicated in the regulation of the actin cytoskeleton. Through this regulation the enzyme controls a number of physiological functions such as cell migration and adhesion and, it also is implicated in the regulation of membrane trafficking. The two phospholipase Ds are closely implicated with the control of the ARF and Rho families of small GTPases. In this article it is proposed that PLD2 plays the role of 'master regulator' and in an ill-defined manner regulates Rho function, PLD1 activity is downstream of this activation, however the generated phosphatidic acid controls changes in cytoskeletal organisation through its regulation of phosphatidylinositol-4-phosphate-5-kinase activity.