Although tuberculosis is an ancient disease, recognition of its airborne route of transmission, with implications for respiratory isolation, is relatively recent. Historically, the disease was believed to be hereditary or contracted by inhaling 'miasma,' or corrupted air, and patients were not routinely isolated. The sanatorium initially served as a place of healing for patients with tuberculosis. Discovery of the tubercle bacillus and its mode of transmission via aerosol in the late 19th/early 20th century reinforced the important public health role of sanatoria and tuberculosis hospitals in preventing disease transmission through isolation. In recent decades, outpatients receiving treatment are required to remain in respiratory isolation at home until they are deemed noninfectious based on multiple sputum samples. This historical review demonstrates that despite changing medical knowledge, drug therapies, and social conditions over time, the role of isolation remains an important topic of debate in the treatment of patients with pulmonary tuberculosis.