Research on stress and disease has often afforded an important role to emotion, typically conceptualized in broad categories (e.g., negative emotions), viewed as playing a causal role (e.g., anger contributing to pathophysiology of cardiovascular disease), and measured using self-report inventories. In this article, I argue for the value of evaluating specific emotions, considering bidirectional causal influences, and assessing actual emotional responding when considering the role that emotions play in the stress-disease relationship. In terms of specificity, specific emotions (e.g., anger, sadness, and embarrassment) can be linked with particular health outcomes (e.g., cardiovascular disease and musculoskeletal disease). In terms of bidirectionality, the influences of emotions on disease as well as the influences of disease on emotional functioning can be considered. In terms of assessing actual emotional responding, emotions can be studied in vivo under controlled conditions that allow behavioral, physiological, and subjective responses to be measured during different kinds of emotional functioning (e.g., responding to emotional stimuli, interacting with relationship partners, and downregulating emotional responses). With these considerations in mind, I review early theories and empirical studies in psychosomatic medicine that considered the role of specific emotions and emotion-related behaviors. Studies from our laboratory are presented that illustrate a) differences in patterns of autonomic nervous system responding associated with specific emotions, b) relationships between specific emotions and particular health outcomes in the context of social relationships, c) age as a moderator of the relationship between specific emotions and well-being, d) bidirectional influences (emotions influencing disease and disease influencing emotional functioning), and e) impact of changes in emotional functioning in individuals with neurodegenerative diseases on the health of familial caregivers.