Polygenic Risk Scores (PRS) (also known as polygenic scores, genetic risk scores or polygenic indexes) capture genetic contributions of a multitude of markers that characterise complex traits. Although their likely application to precision medicine remains to be established, promising advances have included their ability to stratify high risk individuals and targeted screening interventions. Current PRS have been mostly optimised for individuals of Northern European ancestries. If PRS are to become widespread as a tool for healthcare applications, more diverse populations and greater capacity for derived interventions need to be accomplished. In this editorial we aim to attract submissions from the research community that highlight current challenges in development of PRS applications at scale. We also welcome manuscripts that delve into the ethical, social and legal implications that the implementation of PRS may generate.