Oropharyngeal colonization with pathogenic organisms is a near-universal occurrence in critically ill patients receiving mechanical ventilation. Aspiration of these bacteria from the oral cavity and pharynx into the lower respiratory tract contributes to the development of ventilator-associated pneumonia (VAP). Colonization of dental plaque by Gramnegative bacteria has been recognized as an important contributor to the oropharyngeal bacterial pool in ICU patients. Lack of spontaneous movements of the tongue and jaws, reduction of salivary flow, infrequent swallowing, and inability to clean oral cavity and brush teeth because of orotracheal intubation or altered mental status result in biofilm and dental plaque formation. Oral hygiene has been proposed as a key intervention for reducing VAP. Strategies to eradicate oropharyngeal colonization by antiseptic oral care, such as chlorhexidine have been shown to reduce the oral microbial colonization and risk of VAP but failed to reduce duration of mechanical ventilation, ICU length of stay or mortality. Using chlorhexidine for oral antisepsis is simple and inexpensive with a low level of adverse effects but optimal concentration, technique and frequency of application warrant further studies.