This review discusses the evolution and clinical utility of polygenic risk scores (PRS) in the context of common complex disorders. PRS, which combine genetic variants associated with diseases, have been widely used in research to predict disease risk. However, their clinical utility remains uncertain. The review highlights the challenges in translating PRS from research to clinical practice, including the need for better understanding of non-European ancestry, the interpretation of PRS in the context of environmental and clinical factors, and the development of more accurate and clinically actionable PRS. The review also explores the potential applications of PRS in disease prediction, treatment choice, and refining the penetrance of high-risk variants. Despite these challenges, the review suggests that PRS may have significant clinical utility in specific cohorts with a higher prior probability of disease, such as early stages of diseases or high-risk individuals. The authors emphasize the importance of continued research and methodological advancements to improve the clinical relevance and interpretability of PRS.This review discusses the evolution and clinical utility of polygenic risk scores (PRS) in the context of common complex disorders. PRS, which combine genetic variants associated with diseases, have been widely used in research to predict disease risk. However, their clinical utility remains uncertain. The review highlights the challenges in translating PRS from research to clinical practice, including the need for better understanding of non-European ancestry, the interpretation of PRS in the context of environmental and clinical factors, and the development of more accurate and clinically actionable PRS. The review also explores the potential applications of PRS in disease prediction, treatment choice, and refining the penetrance of high-risk variants. Despite these challenges, the review suggests that PRS may have significant clinical utility in specific cohorts with a higher prior probability of disease, such as early stages of diseases or high-risk individuals. The authors emphasize the importance of continued research and methodological advancements to improve the clinical relevance and interpretability of PRS.