Circular RNAs (circRNAs) are highly conserved novel class of endogenous noncoding RNAs. CircRNAs have a stable covalently closed ring structures with no 5′-end cap or 3′-end poly (A) tail. These circular structures are formed by reverse splicing, mainly by means of a noose structure or intron complementary pairing. In clinical applications of cells, exosomes, as a tiny discoid vesicles with a diameter of 40–100 nm that are secreted by cells under physiological and pathological conditions, are considered in recent years. Exosomes play an important role in cell–cell communication by carrying DNA, microRNAs, mRNAs, proteins, and circRNAs. In this chapter, we summarize the biological functions of exosomal circRNAs and further reveal the clinical significance of exosomal circRNAs and their potential roles in different diseases, providing a scientific basis for the diagnosis, treatment, and prognosis of a wide variety of diseases.