In the current cost-attentive health care climate, the effectiveness of various providers in delivering care is being examined closely. To evaluate the effectiveness of respiratory therapists (RTs) in delivering respiratory care in the intensive care unit (ICU), in adult non-ICU inpatient care, and in ambulatory care, this 27th Egan Lecture presents a systematic review of the available literature examining RTs' effectiveness in these settings. Overall, available studies support the effectiveness of RTs in providing care in various roles in all clinical venues, with the strongest evidence based on the results of concordant randomized controlled clinical trials. Indeed, 5 randomized clinical trials show that RTs are effective in implementing respiratory care protocols to wean patients from mechanical ventilation and in appropriately allocating respiratory care services to adult non-ICU inpatients. Lower levels of evidence support RTs' roles in performing intubation, placing indwelling arterial lines, performing mini-bronchoalveolar lavage, allocating arterial blood gases, and in various counseling and teaching roles. Notwithstanding the considerable body of available evidence that buttresses RTs' effectiveness in delivering care, additional rigorously designed studies are needed to examine RTs' effectiveness in new roles (eg, geriatric care, pediatric care), in new venues (eg, extended care facilities), and to assure the generalizability of available findings to the broad spectrum of health care facilities (eg, academic and community-based facilities alike). Finally, the respiratory therapy community must continue to cultivate and suppport investigative expertise to assure continued inquiry.