During cooling of mammalian cells a phase change of the membrane lipids maybe observed by a variety of analytical techniques. This solidification occurs in 2D and the resulting local composition and material properties of the membrane at low temperatures are determined by the rate of cooling. At slow rates a “lipid lateral phase separation” occurs with plaques of gel phase lipid separating out from a more fluid domain, in this event membrane proteins become “freeze concentrated” into the fluid domain. At rapid rates of cooling there is insufficient time for phase separations to occur and a transition analogous to vitrification occurs within the membrane. Low temperature injury of mammalian cells may be classified into two types: Chilling injury This occurs following slow cooling and develops over a period of time (hours) and is associated with a loss of selective permeability of the membrane, possibly by a molecular mismatch at the gel to fluid zone. Cold shock This occurs following rapid cooling and develops immediately and is manifest by immediate membrane leakage and in extreme cases lysis. It has been suggested that cold shock is due to lattice mismatches in the vitrified membrane or to thermomechanical stress. All mammalian membranes are expected to undergo a phase transition before the cells encounter the additional sub-zero stresses associated with preservation. It can be argued that all mammalian cells are susceptible to cold shock. The sensitivity to chilling injury is more variable, some cell-types are stable for extended periods at low temperatures, whilst other cell-types are more sensitive. The specific factors that account for variations in sensitivity are not well understood. Cells from hibernating mammals, invertebrates, plants and microorganisms may display adaptive modifications to membrane composition which confer resistance to low temperatures. These modifications are reviewed and the challenges of implementing such compositional changes to a practical cryopreservation programme are discussed. Finally a range of membrane active materials, including CPA such as DMSO, are reported to increase membrane fluidity and reduce the temperature of membrane phase transitions. In principle these provide a simple route to reducing any cell damage induce by membrane phase behaviour.