The capacity for self-reflection, which plays an important role in human self-regulation, also leads people to become aware of the limitations of their existence. Awareness of the conflict between one's desires (e.g., to live) and the limitations of existence (e.g., the inevitability of death) creates the potential for existential anxiety. In this chapter, we review how this anxiety affects human motivation and behavior in a variety of life domains. Terror management theory and research suggest that transcending death and protecting oneself against existential anxiety are potent needs. This protection is provided by an anxiety-buffering system, which imbues people with a sense of meaning and value that function to shield them against these concerns. We review evidence of how the buffering system protects against existential anxiety in four dimensions of existence: the physical, personal, social, and spiritual domains. Because self-awareness is a prerequisite for existential anxiety, escaping self-awareness can also be an effective way to obviate the problem of existence. After elaborating on how existential anxiety can motivate escape from self-awareness, we conclude the chapter with a discussion of remaining issues and directions for future research and theory development.