Mammalian cells are important for the success of many medical and research endeavors. Unfortunately, these cells are fragile; manipulation or long-term storage often leads to a significant decrease in cell viability. We have developed a novel strategy for protecting mammalian cells using the disaccharide trehalose. Trehalose is a natural cellular protectant that is biosynthesized by organisms such as fungi, insects, and bacteria when they are exposed to stressful conditions. A significant barrier to the introduction of trehalose into mammalian cells is the impermeability of mammalian cell membranes to hydrophilic sugars such as trehalose. We have synthesized cell-permeable analogues of trehalose that deliver high concentrations of free trehalose into mammalian cells. Critically, we have demonstrated that two of these analogues are able to protect mammalian cells from heat shock-induced apoptosis. Currently, I have synthesized a new cell-permeable trehalose analogue, Bu6Tre, and am evaluating it for the ability to deliver trehalose into mammalian cells, as well as its protective effects. Our novel approach for the delivery of trehalose into mammalian cells has the ability to be widely applicable for the protection of mammalian cells exposed to a variety of conditions, ultimately providing a means to improve their longevity during storage, transport, and manipulation.