The presence of miRNAs in biological fluids has been well established. Blood cells are major contributors to circulating miRNAs, and perturbations in their number can alter the circulating miRNA pool (Pritchard et al. 2012; Tonge and Gant 2016). Platelets in particular have been shown to be key contributors as miRNA shedding from platelets has a prominent effect on the circulating miRNA profile, and the levels of many circulating miRNAs are directly related to the platelet activation state (Kaudewitz et al. 2016; Willeit et al. 2013; Zampetaki et al. 2012). Importantly, upon tissue injury, a robust release of tissue-enriched miRNAs is observed in the circulation. A rapid increase in miR-122 levels is detected after liver damage (Wang et al. 2009), while some cardiac miRNAs, e.g. miR-1 and miR-208b, are usually undetectable in the circulation but can be reliably quantified following cardiac injury (Widera et al. 2011). Additionally, circulating miRNA signatures have been proposed to associate with the onset of micro- and macrovascular complications of diabetes (Wang et al. 2016; Zampetaki et al. 2010, 2016) and risk of cardiovascular events (Zampetaki et al. 2012) implying that circulating miRNA fingerprints may have an added value that goes beyond disease diagnosis but also include risk prediction. Intriguingly, if distinct miRNA signatures were to be identified for specific pathologies, circulating miRNA panels may serve as novel biomarkers of disease.