Antimicrobial selection for patients diagnosed with pneumonia is a major therapeutic challenge and dilemma to the clinical practitioner. In the community setting, patients usually receive empiric oral therapy based upon multiple patient risk factors and locally prevalent pathogen susceptibilities. For patients admitted to the hospital with pneumonia, or who acquire pneumonia while in the hospital, therapy can be initially empiric and then become directed once culture and susceptibility results are known. The SENTRY Antimicrobial Surveillance Program since 1997, has monitored pathogen frequency and antimicrobial susceptibilities in hospitalized patients with pneumonia in North America. In this Study 2,712 pathogens were studied from 30 medical centers (25 in the United States and 5 in Canada). Over 30 species of organisms were recovered with Staphylococcus aureus comprising 28.0% of all isolates and with four other species (Pseudomonas aeruginosa 20.0%, Streptococcus pneumoniae 9.1%, Klebsiella spp. 7.5% and Haemophilus influenzae 7.3%) constituted 71.9% of isolates submitted. Methicillin (oxacillin)-resistant S. aureus accounted for 43.7% of all S. aureus isolates. Antimicrobials demonstrating significant (>80%) activity against S. aureus were: chloramphenicol (81.6%), tetracycline (91.4%), rifampin (96.4%) and quinupristin/dalfopristin (99.7%); and no isolate was resistant to glycopeptides or linezolid. North American isolates of P. aeruginosa were most susceptible to amikacin (93.7%) > tobramycin (90.2%) > meropenem (89.1%) > imipenem = piperacillin/tazobactam (85.6%) > piperacillin (82.1%) > cefepime (80.5%). Overall, 32.1% of S. pneumoniae were penicillin non-susceptible while erythromycin susceptibility was only 74.8%. Fluoroquinolones and recent generation cephalosporins retained excellent activity (gatifloxacin [99.2%] > levofloxacin = cefepime [98.8%] > ceftriaxone [97.2%]) against S. pneumoniae. Klebsiella spp. were 100.0% susceptible to the carbapenems (meropenem and imipenem) but extended spectrum beta-lactamases were detected at a rate of 5.4%. The beta-lactamase-positive rate in H. influenzae was 28.6% in North America (71.4% ampicillin-susceptible). The SENTRY Antimicrobial Surveillance Program continues to identify important North American patterns of pathogen frequency and resistance. Additionally, the provision of multi-year longitudinal data and associated reports allow for comparisons, which function as critical tools for effective patient management and antimicrobial interventions.