When do symptoms become a disease? Are there rules or norms, currently or in the past, that tell us when a particular collection of largely symptom-based criteria has enough specificity, utility, or plausibility to justify the appellation disease? The history of numerous symptom-based diagnoses in use today suggests partial answers to these questions. The 19th-century shift to understanding ill health as a result of specific diseases, increasingly defined more by signs than symptoms, led to a loss of status for illnesses that possessed little clinical or laboratory specificity. Nevertheless, clinicians then and now have used symptom-based diagnoses. Some of these diagnoses owe their existence as specific diseases to the norms and practices of an older era much different from our own. Others have not only thrived but have resisted plausible redefinition done by using more “objective” criteria. Many strategies, such as response-to-treatment arguments, quantitative methods (for example, factor analysis), and consensus conferences, have been used to find or confer specificity in symptom-based diagnoses. These strategies are problematic and have generally been used after symptom-based diagnoses have been recognized and defined. These historical observations emphasize that although biological and clinical factors have set boundaries for which symptoms might plausibly be linked in a disease concept, social influences have largely determined which symptom clusters have become diseases.