Circular RNAs (circRNAs) are a novel class of mainly non-coding RNA molecules and have been proposed as promising biomarkers based on their substantially longer half-live compared to other RNA types and their cell-type specific expression patterns. Unfortunately, current circRNA detection pipelines (using RNA-sequencing data) are prone to false positives. As these results propagate to circRNA databases, we are far from a gold standard reference annotation set of circRNAs needed to understand their biogenesis and role in development and disease, and to use them as biomarkers. Here, we propose the development of a toolbox to identify circRNAs with high sensitivity and specificity, including methods to study their function and quantify their biomarker potential in biofluids.