Pseudomonas aeruginosa is a highly adaptable gram-negative bacillus with the ability to cause serious disease in vulnerable populations. This article reviews the relevant epidemiology of this pathogen in the hospital setting with particular attention to the neonatal unit. Issues related to reservoirs of the organism with special consideration of the hands of staff are also addressed. Virulence factors and pathogenic mechanisms are highlighted as well as the important role of antimicrobial resistance patterns. Finally, there is a discussion of the clinical syndromes found in neonates and the appropriate antibiotic usage strategies for effective treatment of this pathogen of continuing importance.