The binding of vascular endothelial growth factor (VEGF) to its receptors (VEGFR1 and VEGFR2) on endothelial cells can induce many effects, including proliferation, migration and angiogenesis, through the activation of several intracellular signalling pathways. For example, Debabrata Mukhopadhyay and colleagues showed in a previous study that VEGF induces the lipase activity of phospholipase Cγ1 (PLCγ1) and PLCβ3. Whereas PLCγ1 activation is known to have a role in VEGF-induced DNA synthesis, the role of PLCβ3 downstream of VEGF has been unclear. Now, Mukhopadhyay and colleagues (p. 1025) use RNA-interference techniques to show that PLCβ3 promotes directional migration and inhibits proliferation downstream of VEGFR2 in endothelial cells. They show that the pro-migratory function of PLCβ3 involves its effects on actin reorganisation and its capacity to activate the small GTPase Cdc42, and that PLCβ3 inhibits proliferation through effects on the cell cycle. Therefore, the authors conclude that PLCβ3 is important in the context of angiogenesis by promoting a pro-migratory and anti-proliferative phenotype in endothelial cells.