Lipid and glycolipid mediators are important components 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 apoptotic 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. Interestingly, GD3 expression also increases with the normal ageing process. Moreover, GD3 can also mediate biological events like proliferation and differentiation. Since organism integrity requires a tight balance between cell proliferation, apoptosis and senescence, controlling the intracellular level of GD3 appears of particular importance for cell fate determination.