Phosphoinositides are a family of phosphorylated derivatives of the membrane lipid phosphatidylinositol. These lipids are highly concentrated in distinct pools located in a cell's plasma membrane, endosomes or nucleus, where they function as ligands for phosphoinositide-binding proteins. Protein domains that bind phosphoinositides include the pleckstrin homology (PH) domain, the phox homology (PX) domain and the Fab1p-YOPB-Vps27p-EEA1 (FYVE) domain. These domains are found in many proteins involved in intracellular signaling, membrane trafficking and cytoskeletal rearrangement. Recent studies have identified potential links between alterations to various signaling pathways involving phosphoinositides and the etiology of many human diseases.