Rationale: Controversy still exists in the international literature regarding the need to use antimicrobials covering atypical pathogens when initially treating hospitalized patients with community-acquired pneumonia(CAP). In different regions of the world, monotherapy with a beta-lactam antimicrobial is common. Objectives: We sought to correlate the incidence of CAP due to atypical pathogens in different regions of the world with the proportion of patients treated with an atypical regimen in those same regions. In addition, we sought to compare clinical outcomes of patients with CAP treated with and without atypical coverage. Methods: A secondary analysis was performed using two comprehensive international databases. World regions were defined as (I)North America, (II)Europe, (III)Latin America, (IV)Asia and Africa. Time to reach clinical stability, length of hospital stay (LOS), and mortality were compared between patients treated with and without atypical coverage. Measurements and Main Results: The incidence of CAP due to atypical pathogens from 4,337 patients was 22%, 28%, 21% and 20% in regions I-IV, respectively. The proportion of patients treated with atypical coverage from 2,208 patients was 91%, 74%, 53% and 10% in regions I-IV, respectively. Patients treated with atypical coverage had decreased time to clinical stability (3.7 vs. 3.2 days, P<0.001), decreased LOS (7.1 vs. 6.1 days, P<0.01), decreased total mortality (11.1% versus 7%, P<0.01), and decreased CAP-related mortality (6.4% versus 3.8%, P<0.05). Conclusions: The significant global presence of atypical pathogens and the better outcomes associated with antimicrobial regimens with atypical coverage support empiric therapy for all hospitalized patients with CAP with a regimen that covers atypical pathogens.