The diversity of RNA classes identified in platelets has expanded significantly over the past decade. Beyond coding messenger RNAs, the platelet transcriptome includes a variety of non-coding RNAs (ncRNAs) including microRNAs, YRNAs, long non-coding RNAs and circular RNAs. Platelet ncRNAs may exert functions both within and outside of platelets. Platelets contribute substantially to the extracellular circulating ncRNA pool, with their ncRNAs being protected from extracellular degradation by protein or vesicle carriers. Circulating levels of platelet-derived ncRNAs have been linked to measures of platelet activation and the effects of antiplatelet therapy, positioning them as potential novel markers of platelet reactivity. Unlike ex vivo platelet function tests, ncRNA profiling may allow in vivo assessment of platelet reactivity. However, it remains uncertain whether ncRNAs will have a role in routine clinical diagnostics. Major challenges in platelet ncRNA research include susceptibility to preanalytical variability, a lack of standardized protocols for sample preparation, and inconsistent data normalization methods, all of which limit the comparability of studies.