Lipid and glycolipid mediators are important messengers of the adaptive responses to stress, including apoptosis. In mammalian cells, the intracellular accumulation of ganglioside GD3, an acidic glycosphingolipid, contributes to mitochondrial damage, a crucial event during the apoptopic program. GD3 is a minor ganglioside in most normal tissues. Its expression increases during development and in pathological conditions such as cancer and neurodegenerative disorders. Intriguingly, GD3 can mediate additional biological events such as cell proliferation and differentiation. These diverse and opposing effects indicate that tightly regulated mechanisms, including 9-O-acetylation, control GD3 function, by affecting intracellular levels, localization and structure of GD3, and eventually dictate biological outcomes and cell fate decisions.