Although clinically useful, the conventional partition of diabetes mellitus into two major classes, insulin dependent and non-insulin dependent, has become obsolete from an etiological standpoint. Contemporary research, particularly that with advanced cellular and molecular methodologies, suggests that the expression of diabetes depends on a wide range of factors. We suggest that the etiology of diabetes has become analogous to the cylinder of a lock containing many tumblers. Each tumbler, e.g., environment, genetics, or cellular interactions, must be aligned before the key can be turned and an understanding of the etiologic process claimed.