By far the largest proportion of the Earth's biosphere is comprised of organisms that thrive in cold environments (psychrophiles). Their ability to proliferate in the cold is predicated on a capacity to synthesize cold-adapted enzymes. These enzymes have evolved a range of structural features that confer a high level of flexibility compared to thermostable homologs. High flexibility, particularly around the active site, is translated into low-activation enthalpy, low-substrate affinity, and high specific activity at low temperatures. High flexibility is also accompanied by a trade-off in stability, resulting in heat lability and, in the few cases studied, cold lability. This review addresses the structure, function, and stability of cold-adapted enzymes, highlighting the challenges for immediate and future consideration. Because of the unique properties of cold-adapted enzymes, they are not only an important focus in extremophile biology, but also represent a valuable model for fundamental research into protein folding and catalysis.