Pneumonia in elderly patients is a major public health concern because of greater morbidity and mortality and longer hospital stays relative to younger populations. Based on the premise that osteopathic manipulative treatment (OMT) is beneficial in the management of pulmonary infections, the Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) was designed as a prospective randomized controlled trial to evaluate the efficacy of OMT as an adjunct to the current pharmacologic treatment of elderly patients hospitalized for pneumonia. The protocol developed for MOPSE has its origins in early osteopathic medical literature at a time when effective antibiotic therapy was unavailable and osteopathic physicians relied on physical examination and empiric reasoning to develop treatment strategies and OMT techniques to improve host defenses against pneumonia. The present paper reviews the early osteopathic medical literature to identify the reasoning behind the OMT techniques that are the basis for the design of the MOPSE protocol. Likewise, the contemporary medical literature relevant to the protocol is reviewed. Finally, a description of the study design and the OMT and light touch (sham) protocols used in MOPSE are provided.