Modern anxiety disorder models implicitly include intolerance of uncertainty (IU) as a critical component for the development and maintenance of these pervasive social and economic concerns. IU represents, at its core, fear of the unknown - a long-recognized, deep-seated fear identified in normative and pathological samples. Indeed, the intrinsic nature of IU can be argued as evolutionarily supported, a notion buttressed by initial biophysiological evidence from uncertainty-related research. Originally thought to be specific to generalized anxiety disorder, recent research has clearly demonstrated that IU is a broad transdiagnostic dispositional risk factor for the development and maintenance of clinically significant anxiety. The available evidence suggests that theorists, researchers and clinicians may benefit from explicitly incorporating IU into models, research designs, case conceptualizations and as a treatment target.