Although many new antiseizure drugs have been developed in the past decade, approximately 30%–40% of patients remain pharmacoresistant. There are no clinical tools or guidelines for predicting therapeutic response in individual patients, leaving them no choice other than to try all antiseizure drugs available as they suffer debilitating seizures with no relief. The discovery of predictive biomarkers and early identification of pharmacoresistant patients is of the highest priority in this group. MicroRNAs (miRNAs), a class of short noncoding RNAs negatively regulating gene expression, have emerged in recent years in epilepsy, following a broader trend of their exploitation as biomarkers of various complex human diseases. We performed a systematic search of the PubMed database for original research articles focused on miRNA expression level profiling in patients with drug-resistant epilepsy or drug-resistant precilinical models and cell cultures. In this review, we summarize 17 publications concerning miRNAs as potential new biomarkers of resistance to antiseizure drugs and their potential role in the development of drug resistance or epilepsy. Although numerous knowledge gaps need to be filled and reviewed, and articles share some study design pitfalls, several miRNAs dysregulated in brain tissue and blood serum were identified independently by more than one paper. These results suggest a unique opportunity for disease monitoring and personalized therapeutic management in the future.