Differentiation of self involves the capacity to modulate affect, maintain a clear sense of self, and balance intimacy and autonomy in significant relationships. Given the central role of family relationships for individual functioning, the authors tested whether differentiation mediated or moderated relations between college stress and personal adjustment. Differentiation of self partially mediated effects of academic and financial stress and exerted a direct influence on adjustment. Limitations, directions for future research, and implications for counseling are discussed.