This article focuses on the emerging roles for phosphatidylinositol 4-phosphate and the phosphatidylinositol 4-kinases in cancer. Phosphatidylinositol 4-phosphate is a common substrate for both the phosphatidylinositol 3-kinase and phospholipase C pathways, and has been implicated in the membrane targeting of proteins such as Girdin/GIV and OSBP. Alterations to phosphatidylinositol 4-kinase expression levels can modulate MAP kinase and Akt signalling, and are important for chemoresistance, tumour angiogenesis and the suppression of apoptosis and metastases. Recent improvements in high-throughput screening assays, and the discoveries that some anti-viral molecules are isoform selective phosphatidylinositol 4-kinase inhibitors have advanced the drugability of these enzymes.