Neuroticism and conscientiousness have emerged as key concepts in understanding health and thriving as individuals age, but various conceptual misunderstandings and methodological deficiencies have impaired progress. Personality traits are not analogous to health threats such as infectious microbes or dangerous behaviors or environmental toxins; rather, they can capture biopsychosocial processes across time. This article examines how healthy neuroticism and unhealthy neuroticism play out in differing environments and how these concepts can help clarify and explain the important variability in health and longevity that emerges in middle age. Progress in utilizing personality to improve public health ultimately will depend on the precise study and full specification of causal models, including pathways across time and clear description of unambiguous outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).