The crystallins were discovered as the structural proteins of the vertebrate eye lens in the last century by C.T. Mörner (Z. Physiol. Chem. 18, 1893, 61-106). Since that time the mammalian crystallins referred to as alpha-, beta-, and gamma-crystallins have been characterized with respect to their genetic organization, the regulation of their expression pattern and their participation in several diseases. Moreover, some crystallins have also been discovered outside the eye. Evolutionary analysis has demonstrated the relationship of crystallins to proteins involved in protection against stress. The alpha-crystallins are considered to be molecular chaperones and members of the small heat shock protein family; they have autokinase activity and are involved in the gamma-crystallin gene activation. The alpha-crystallins are associated with a broad variety of neurological disorders. The beta/gamma-crystallin superfamily is characterized by four greek key motifs. The various N- and C-terminal extensions of the beta/gamma-crystallins are mainly responsible for their distinct biophysical and biochemical properties. Modifications in the beta/gamma-crystallins or mutations in their genes lead to opacification of the eye lens (cataract). Other proteins found to be expressed at relatively high levels in the lens are characterized bytheir strong relationship to well-known enzymes. They are referred to as enzyme-crystallins, and as one example, the xi-crystallin will be discussed. It has evolved from a quinone oxidoreductase using a lens-specific promoter, and a mutation in xi-crystallin is involved in cataract formation.