Phospholipase D (PLD) hydrolyzes structural phospholipids of biological membrane to produce phosphatidic acid (PA) and a free-head group. Both of these compounds can participate in signal transduction. Since the activation of PLD involved in many cellular signaling cascades was identified in recent years, knowledge of and interest in PLD have grown greatly, and significant progress has been made toward understanding PLD. This paper reviewed the research progress on gene structure, regulation and cellular function of PLD. PLDs are encoded by a multiple heterogenous gene family. The overall domain structures of plant PLDs are similar, but important differences occur in some of the motifs. The small structural variations underlie distinct regulatory and catalytic properties and cellular function in signaling. PA and other messengers produced by other phospholipase pathways can be interconverted with the action of lipid kinase and phosphatase. PLD is thought to function as an integral part of a network involving other lipid-signaling enzymes and messengers. Some research evidence demonstrated the specificity of PLDs in signal transduction with plant species, cell types, stimuli and cellular processes. Some important questions about PLD study were also raised.