Root canal treatment is a frequently performed procedure aimed to address pulpal and peri-radicular disease. It comprises a number of clinical steps regardless of the initial diagnosis. The emphasis of each step varies according to whether there is a vital pulp (non-infected) or if the pulp system contains necrotic, infected tissue and there is peri-apical pathology. This article aims to discuss the differences in performing root canal treatments on teeth with vital and non-vital pulps. The reader should understand the differences between performing a root canal treatment in teeth with vital pulps and those with infected root canal spaces and peri-radicular pathology.