Genome-Wide Association Studies (GWAS) are the primary method used to investigate the effects of common genetic variants on health and disease and are increasingly used as an arena for applied epidemiological methods. There are now a growing number of applications of GWAS in oral health research, yielding exciting findings and holding great potential for future discoveries. While exciting, the GWAS approach has inherent limitations, and the success of these experiments depends on achieving adequate statistical power. In the context of dental diseases, where multiple genetic variants have small effects, very large samples are needed to unlock the full potential of GWAS. This article discusses the motivation for undertaking these studies, introduces the GWAS method, and highlights the potential of GWAS to help unravel the complex factors influencing oral health and diseases. Alongside the promises of GWAS, this article also summarizes the key challenges that need to be addressed for this method to be deployed usefully and suggests criteria to consider during the appraisal of a GWAS paper.