Small non-coding PIWI-interacting RNAs (piRNAs) silence the expression of transposable elementsof eukaryotic genomes in germline cells. Additionally, piRNAs regulate chromatin modifications, such as trimethylation of histone H3 lysine 9 (H3K9me3) or DNA methylation. In the past decade, the roles of piRNAs have been characterized in somatic cells, including post-mitotic neurons. More recently, piRNAs have been shown to play important roles in brain functions and various neuronal diseases, including neurodegenerative disorders. In this review, we introduce recent findings showing the potential involvement of piRNAs in the etiology of different neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). These pioneering studies on disease-associated small RNAs will contribute to improving our understanding of the pathogenesis of these neurodegenerative diseases and the development of novel therapeutic strategies.