Abstract A successful endodontic treatment requires a combination of satisfactory mechanical instrumentation, adequate irrigation protocols, and three-dimensional obturation of the canal system. Irrigation is considered the most critical procedure to ensure cleaning and disinfection. To date, a large variety of irrigants has been proposed. However, sodium hypochlorite (NaOCl) remains the gold standard. In order to achieve complete cleaning and disinfection, final irrigation with EDTA and ultrasonic devices has been used as an ideal protocol. Most endodontic research focuses on the cleaning and antibacterial properties of the irrigant solutions. Recent evidence demonstrated that the irrigation protocols cause erosion, affecting the radicular dentin ultrastructure. This article aims to describe the clinical features of the present knowledge concerning the effect of irrigation protocols on radicular dentin.