Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well. With increasing representation of global populations in genetic studies, there is an opportunity for advanced methods development and a need for consensus “best practices” for analyzing datasets. We provide background on the scientific and ethical importance of including underrepresented groups in genetics research and offer guidance for genome-wide analysis of ancestrally diverse study cohorts.