More than a century has elapsed since the initial description of sarcoidosis, but critical aspects of the disorder remain poorly understood. Information obtained from epidemiologic observations and basic laboratory research suggests that the disease may represent an immunologic response to an exogenous agent in a genetically susceptible individual. However, a definitive etiologic role for any specific exogenous agent has never been proved, and a “candidate gene” underlying a predisposition to sarcoidosis has not yet been identified. This review presents an historical framework for considering available evidence regarding a transmissible agent in sarcoidosis and host susceptibility to the disease.