Phosphorylated derivatives of the phospholipid phosphatidylinositol, or phosphoinositides, are implicated in many aspects of cell function. Binding of phosphoinositides that are localized within cell membranes to soluble protein ligands allows spatially selective regulation at the cytoplasm-membrane interface. Recently, studies that relate phosphoinositide production to membrane domains are converging with those that show effects of these lipids on the assembly of cellular actin, and are therefore linking membrane and cytoskeletal structures in new ways.