The etiology of generalized anxiety disorder (GAD), including its high degree of comorbidity with major depressive disorder (MDD), remains a conceptual and clinical challenge. In this article, we discuss the relevance of regulatory focus theory, an influential theory of self-regulation, for understanding vulnerability to GAD as well as GAD/MDD comorbidity. The theory postulates two systems for pursuing desired end states: the promotion and prevention systems. Drawing upon studies documenting the affective and motivational consequences of failing to attain promotion versus prevention goals, as well as the literature linking promotion failure with depression, we propose how dysfunction within the prevention system could lead to GAD -with, as well as without, MDD.