The wide-ranging cellular effects of phosphoinositides are mediated through their interaction with proteins containing lipid-binding modules such as pleckstrin homology and FYVE domains. Recent work has revealed that the PX domain — a domain first identified in NADPH oxidase subunits several years ago — is also a phosphoinositide-binding module. On p. 1099, Chris Ellson and co-workers discuss studies that are shedding light on the structure and function of this domain, which in most cases is specific for PtdIns(3)P. NMR and X-ray crystallography have revealed that the PX domain has a novel `wedge-like' fold in which one face forms the phosphoinositide-binding pocket; these studies are also beginning to establish the residues that determine ligand binding specificity. The domain is most common in proteins involved in membrane trafficking — for example, the t-SNARE Vam7p and sorting nexins. It appears to target these proteins to PtdIns(3)P-rich membranes. The latter include endosomes and vacuoles,in which PtdIns(3)P levels do not vary, as well as phagosomes, in which PtdIns(3)P levels are regulated by external stimuli.