The human genome contains numerous genetic polymorphisms contributing to different health and disease outcomes. Tandem repeat (TR) loci are highly polymorphic yet under-investigated in large genomic studies, which has prompted research efforts to identify novel variations and gain a deeper understanding of their role in human biology and disease outcomes. We summarize the current understanding of TRs and their implications for human health and disease, including an overview of the challenges encountered when conducting TR analyses and potential solutions to overcome these challenges. By shedding light on these issues, this article aims to contribute to a better understanding of the impact of TRs on the development of new disease treatments.