The promise of personalized medicine is highly dependent on the identification of biomarkers that inform diagnostic decisions and treatment options, as well as on the accurate, rapid and cost-effective detection and interpretation of these biomarkers. miRNAs, which are short noncoding regulatory RNAs, are rapidly emerging as a novel class of biomarkers with a unique set of biological and chemical properties that makes them very appealing candidates for theranostic applications in cancer. Since the utility of some protein-encoding gene biomarkers is already exploited in routine clinical practice, it will be important to identify areas in which miRNAs provide complementary or superior information to these existing (and other translational) biomarkers to enhance the diagnostic, prognostic and predictive power of molecular characterization of tumors. In this article, the challenges and opportunities for integration of miRNA-based assays in the clinical toolkit to improve care and management of patients afflicted with solid tumors will be discussed.