This study explored challenges and stressors facing academic deans within higher education. The study analyzed, via step-wise multiple regression, the degree to which current challenges and related stress were associated with the well-being measures of effort-reward imbalance and over-commitment as measured by the Effort/Reward Imbalance scale (ERI); hardiness, as measured by the Dispositional Resilience Scale (DRS); and aspects of burnout, as measured by the Maslach Burnout Inventory (MBI). Results indicated that the stress related to certain challenges (e.g., balancing financial resources, creating a clear vision, promoting change) have particularly powerful influences on aspects of work well-being. Implications and recommendations are included.