Recent studies have clearly demonstrated that estrogen signaling is not limited by the canonical 'genomic' pathway. Estrogens have been shown to interact with multiple cytoplasmic signaling networks including that of growth factors, cytokines, and the most recently recognised participants, sphingolipids. Sphingosine kinase (SphK), a key enzyme in metabolic pathways of sphingolipids, plays an important role in cell signaling and regulates a wide range of biological functions, including the actions of estrogens. Herein we briefly review current experimental evidence showing a critical involvement of sphingolipids in estrogen signaling, especially in breast cancer and vascular endothelial cells. In the current review we mainly focus on the SphK pathway and discuss the potential role of SphK and sphingolipids in the cellular biology of estrogens.