There is a major unmet need for biomarkers of epilepsy. Biofluids such as blood offer a potential source of molecular biomarkers. MicroRNAs (miRNAs) fulfill several key requirements for a blood‐based molecular biomarker being enriched in the brain and dysregulated in epileptic brain tissue, and manipulation of miRNAs can have seizure‐suppressive and disease‐modifying effects in preclinical models. Biofluid miRNAs also possess qualities that are favorable for translation, including stability and easy and cheap assay techniques. Herein we review findings from both clinical and animal models. Studies have featured a mix of unbiased profiling and hypothesis‐driven efforts. Blood levels of several brain‐enriched miRNAs are altered in patients with epilepsy and in patients with drug‐resistant compared to drug‐responsive seizures, with encouraging receiver‐operating characteristic (ROC) curve analyses, both in terms of sensitivity and specificity. Both focal and generalized epilepsies are associated with altered blood miRNA profiles, and associations with clinical parameters including seizure burden have been reported. Results remain preliminary, however. There is a need for continued discovery and validation efforts that include multicenter studies and attention to study design, sample collection methodology, and quality control. Studies focused on epileptogenesis as well as associations with covariables such as sex, etiology, and timing of sampling remain limited. We identify 10 knowledge gaps and propose experiments to close these. If adequately addressed, biofluid miRNAs may be an important future source of diagnostic biomarkers that could also support forthcoming trials of antiepileptogenesis or disease‐modifying therapies.