Numerous organisms are capable of surviving more or less complete dehy
dration. A common feature in their biochemistry is that they accumulat
e large amounts of disaccharides, the most common of which are sucrose
and trehalose. Over the past 20 years, we have provided evidence that
these sugars stabilize membranes and proteins in the dry state, most
likely by hydrogen bonding to polar residues in the dry macromolecular
assemblages. This direct interaction results in maintenance of dry pr
oteins and membranes in a physical state similar to that seen in the p
resence of excess water. An alternative viewpoint has been proposed, b
ased on the fact that both sucrose and trehalose form glasses in the d
ry state. It has been suggested that glass formation (vitrification) i
s in itself sufficient to stabilize dry biomaterials. In this review w
e present evidence that, although vitrification is indeed required, it
is not in itself sufficient. Instead, both direct interaction and vit
rification are required. Special properties have often been claimed fo
r trehalose in this regard. In fact, trehalose has been shown by many
workers to be remarkably (and sometimes uniquely) effective in stabili
zing dry or frozen biomolecules, cells, and tissues. Others have not o
bserved any such special properties. We review evidence here showing t
hat trehalose has a remarkably high glass-transition temperature (T-g)
. It is not anomalous in this regard because it lies at the end of a c
ontinuum of sugars with increasing T-g, However, it is unusual in that
addition of small amounts of water does not depress T-g, as in other
sugars. Instead, a dihydrate crystal of trehalose forms, thereby shiel
ding the remaining glassy trehalose from effects of the added water. T
hus under less than ideal conditions such as high humidity and tempera
ture, trehalose does indeed have special properties, which may explain
the stability and longevity of anhydrobiotes that contain it. Further
, it makes this sugar useful in stabilization of biomolecules of use i
n human welfare.