It is very important to obtain a tight seal in obturated root canal, making it necessary to conduct clinical or laboratory studies on the sealability of endodontic materials. Different methodologies have been historically used to assess microleakage of different endodontic materials. The aim of the present study was to comprehensively review different material testing methods used in microleakage studies, their interpretation and importance in endodontic literature. A systematic search was conducted in Medline, Cochrane, and Web of Science databases. In addition, the reference lists of review articles on the topic were searched. No language restriction was applied. Two independent reviewers screened the article. Microleakage is considered the single most important risk factor responsible for apical periodontitis. Dye penetration, dye diffusion, bacterial and endototoxin infiltration, fluid filtration, glucose, caffeine and protein infiltration, radioisotope penetration, animal studies, and electrochemical or 3D evaluation are different methodologies used to assess dental leakage. 91 out of 177 articles in the primary search were included in the study. These methods are very divergent in their viewpoints; that is why their results cannot be easily compared. It is necessary to standardize microleakage detection methods in order to more correctly evaluate the phenomena that are found between the root canal wall and the root canal filling materials. All the methods are useful if studies are performed strictly with large sample sizes and proper control groups and if the technique can be standardized. Furthermore, more evaluations of the reliability of the methods are strongly recommended.