Ventilator-associated pneumonia is preceded by lower-respiratory-tract colonization by pathogenic microorganisms that derive from endogenous or exogenous sources. Most ventilator-associated pneumonias are the result of exogenous nosocomial colonization, especially, pneumonias caused by resistant bacteria, such as methicillin-resistant Staphylococcus aureus and multi-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, or by Legionella species or filamentous fungi, such as Aspergillus. Exogenous colonization originates from a very wide variety of animate and inanimate sources in the intensive care unit environment. As a result, a strategic approach that combines measures to prevent cross-colonization with those that focus on oral hygiene and prevention of microaspiration of colonized oropharyngeal secretions should bring the greatest reduction in the risk of ventilator-associated pneumonia. This review examines strategies to prevent transmission of environmental pathogens to the vulnerable mechanically-ventilated patient.