In the past many in vitro studies were presented on the efficiency of the apical closure of the root canal. Such studies are relatively easy to perform in contrast to clinical studies. In order to determine which type of apical seal will give the best result, many techniques are evaluated. These results from in vitro studies are difficult to apply to the clinical situation. The results of clinical studies on root canal treatments are not always in accordance with the findings of in vitro studies. It remains a challenge to design a research protocol with an improved predictive value for the clinical situation