MicroRNAs (miRNAs) are master regulators of gene expression. By degrading or blocking translation of messenger RNA targets, these non-coding RNAs can modulate the expression of more than half the protein-coding genes in mammalian genomes. MiRNAs play important regulatory roles in a variety of cellular functions and in several diseases, including cancer. Aberrant miRNA expression has been well characterized in cancer, with implications for progression and prognosis. Recently, the discovery of miRNAs in body fluids, such as serum and plasma, opens up the possibility of using them as noninvasive biomarkers of disease and therapy response. In this chapter, we discuss the use of circulating miRNAs as biomarkers of disease and therapy response and as diagnostic and prognostic markers in breast cancer. We also discuss the main issues related to establishing circulating miRNAs as biomarkers in cancer.