Introduction: Although transmission of infection during endoscopy is an extremely rare event, most cases reported have been associated with failure to employ appropriate cleaning, disinfection/sterilization, rinsing and drying of endoscopes. Methods: The medical literature was reviewed to evaluate the transmission of specific infection during endoscopic procedures; furthermore, this article focuses on the characteristics, advantages and disadvantages of the principal chemical compounds used for high level disinfection. Results: This review identified several published reports and clinical studies that demonstrate the endoscopic transmission of various bacterial infections. In this regard, Pseudomonas aeruginosa is the most commonly reported organism responsible for transmission of infection during endoscopy, whereas Salmonella species transmission does not appear to be a persistent control problem after the introduction of standardized cleaning and disinfection guidelines; moreover, cases of Helicobacter pylori endoscopic infection have been reported and have been mainly attributed to suboptimal endoscopes' cleaning and disinfection. However, the adoption of current reprocessing protocols is sufficient to eradicate the specific organism. On the other hand, endoscopic transmission of Mycobacterium tuberculosis is a rare event since only two cases of infection have been reported to date. Additionally, other clinically significant viruses continue to be transmitted, with low transmission rate, by gastrointestinal endoscopy, including hepatitis C, and hepatitis B, whereas no cases of HIV transmission have been reported in the world literature. In order to prevent the spread of healthcare-associated infections, all heat sensitive endoscopes must be properly cleaned and subjected to high level disinfection following each use. Although the ideal chemical sterilant does not exist, several high-level disinfectants have been developed. One of the most used sterilants is glutaraldehyde but its use is associated with respiratory problems and skin irritations. The last years, several chemical sterilants have been developed including 7.5% hydrogen peroxide, 0.08% peracetic acid plus 1.0% hydrogen peroxide. However, both of the above sterilants present material compatibility concerns. Another new product with excellent microbiocidal activity is 0.55% orthophthalaldehyde that has potential advantages. Other chemical sterilants developed are Aldahol III και Acecide™; main restriction of the above products is the high cost. Conclusions-Discussion: Although the incidence of infection related to endoscopic procedures is low, endoscopes' high level disinfection is a process that renders a contaminated endoscope safe for reuse. This article by reviewing the medical literature could aid the infection control professionals in choosing the appropriate disinfection methodology. Selection of a product must be weighed against the needs of a particular setting taking into consideration factors such as compatibility, microbiocidal spectrum, toxicity and cost.