Circular RNAs (circRNAs) have garnered considerable attention in recent years as potential biomarkers for liquid biopsies due to their unique characteristics offering unique advantages over linear RNAs. The significance of circRNAs, highlighting their stability, abundant expression, noninvasiveness, and cell/tissue specificity, makes circRNAs appealing candidates for liquid biopsies, facilitating real-time disease monitoring and guiding treatment decisions. Advancements in high-throughput RNA sequencing and experimental technologies have facilitated extensive identification and characterization of blood circRNAs (cell-free circRNAs and circRNAs in blood cells), revealing their roles in various human diseases. This chapter delves into the diverse roles of blood circRNAs across a spectrum of human diseases, including cancer, cardiovascular diseases, autoimmune disorders, neurological conditions, and pregnancy-related complications and shedding light on their cellular functions and regulatory mechanisms. It worth mentioning that individual circRNAs may sometimes lack sufficient sensitivity and specificity, necessitating the use of combinations for enhanced diagnostic value. Overall, it can be concluded that blood circRNAs hold immense promise as diagnostic and prognostic biomarkers in various human diseases. However, continued research efforts are needed to elucidate their full potential, optimize detection methods, and develop standardized diagnostic assays. By leveraging the unique properties of circRNAs, liquid biopsy approaches can revolutionize disease management, improve patient care, and ultimately enhance clinical outcomes.