Sphingolipids were first described more than 100 years ago by the physician Thudicum who named the fatty substance he found in brain 'sphingosin'. Among multiple other functions, sphingolipids are lipid messengers in the signaling pathways of growth factors, cytokines, cellular stresses and others. As such, they are involved in the regulation of a wide spectrum of processes that modulate cell growth and cell death. These functions may be beneficial in cancer cells that escape growth regulation and exhibit unlimited proliferation. The effects of exogenous sphingolipids on cancer cells in vitro have been well documented; however, the effects of sphingolipids in vivo are less well understood. Since the mechanisms sphingolipids utilize in the prevention of cancer may be different from those in cancer treatment- modulation of cell growth versus induction of cell death- this review will focus on the known effects of orally administered sphingolipids in the prevention of colon cancer in different rodent models, and discuss the effect of sphingolipid metabolites on changes in cell proliferation and cell death that are important events in early carcinogenesis.