There are numerous studies that suggest multiple links between the cellular phosphoinositide system and cancer. As key roles in cancer have been established for PI3K and PTEN - enzymes that regulate the levels of phosphatidylinositol-3,4,5-trisphosphate - compounds targeting this pathway are entering the clinic at a rapid pace. Several other phosphoinositide-modifying enzymes, including phosphoinositide kinases, phosphatases and phospholipase C enzymes, have been implicated in the generation and progression of tumours. Studies of these enzymes are providing new insights into the mechanisms and the extent of their involvement in cancer, highlighting new potential targets for therapeutic intervention.