Non-coding RNAs (ncRNAs), and in particular microRNAs are rapidly becoming the focus of research interest in numerous basic and translational fields, and their importance for many aspects in brain functioning merits special discussion. The wide-scope, multi-targeted and highly efficient manner of ncRNA regulatory activities draws attention to this topic by many, but the available research tools and experimental protocols are still insufficient, and their importance for many aspects in brain functioning merits special discussion. This Research Topic is focused on the search for and exploration of those non-coding RNAs whose activities modulate the multi-leveled functions of the eukaryotic brain. It will strive to cover novel approaches for identifying and establishing ncRNA-target relationships, reports of the affected pathways, inherited and acquired changes in ncRNA functioning and the use of ncRNA mimics and blockade tools for interference with their functions in health and disease. Non-coding RNAs are here to stay, and their impact on our brain’s functioning at the physiology, cell biology, behavior and immune levels is worth an in-depth journey.