This chapter examines evidence linking perfectionism with difficulties in coping with chronic illness—an assessment that highlights how excessive striving for perfection may be a liability in the context of ongoing health limitations. It focuses on key mechanisms and processes that render certain perfectionists particularly vulnerable to health problems. The chapter proposes two potential pathways that may help further our understanding of why perfectionism might be implicated in poor health outcomes, namely stress and health behaviors. It is important to note at the outset that we view perfectionism as reflecting a behavioral pattern and cognitive, emotional, and motivational orientation toward a form of hyper-conscientiousness that is distinguishable from conscientiousness. Although the study of perfectionism in chronic illness is in its infancy, both theory and preliminary empirical evidence suggest that perfectionism plays an important role in the etiology and maintenance of several chronic illnesses.