Altered sphingolipid metabolism contributes to cancer progression and presents an exploitable target for the development of novel chemotherapeutics. Bioactive sphingolipid metabolites also have the potential to serve as vital biomarkers for cancer and be utilized to determine disease progression, as well as guide therapeutic regimens. Moreover, identification of these sphingolipid biomarkers is achievable based on recent technological advances in sphingolipidomics, which have aided in detection of sphingolipid metabolites through tools like mass spectrometry. Excellent reviews have previously focused on the biochemical role that sphingolipids have in cancer pathogenesis and treatment. The aim of this review is to concentrate on the critical metabolites and enzymes that contribute to the dysregulation in sphingolipid metabolism, and highlight relevant translational research that is directed towards novel therapies.