The present article reviews the association between microbial colonization of the oral cavity and the lungs in critically ill patients that develop ventilator-associated pneumonia (VAP) in the intensive care unit (ICU) setting. The risk factors and microorganisms associated with VAP are presented. The role of oral colonization of VAP-associated pathogens (VAP-AP) in the development of VAP is examined. We explore the potential factors involved in oral colonization of VAP-AP, which are atypical bacteria for the oral cavity. Strategies for the prevention or moderation of oral colonization of VAP-AP have had limited success. We need a deeper understanding of the pathophysiology of VAP in order to reduce the morbidity, mortality, and cost from this common complication in ICU medicine and surgery.