The root canal system is colonised with microorganisms in cases of apical periodontitis. Currently, it is impossible to totally eliminate these microbes purely with mechanical instrumentation. Therefore, irrigants are required to eradicate intraradicular infection. In this article, the different actions and interactions of the most commonly used irrigants are discussed and a clinical protocol suggested. At least two different irrigants should be used to achieve the most effective reduction of intraradicular microorganisms. Keywords: apical periodontitis, chlorhexidine, disinfection, smear layer, sodium hypochlorite