Neurodegenerative diseases are typically late-onset, progressive disorders that affect neural function and integrity. Although most attention has been focused on the genetic underpinnings of familial disease, mechanisms are likely to be shared with more predominant sporadic forms, which can be influenced by age, environment, and genetic inputs. Previous work has largely addressed the roles of select protein-coding genes; however, disease pathogenesis is complicated and can be modulated through not just protein-coding genes, but also regulatory mechanisms mediated by the exploding world of small non-coding RNAs. Here, we focus on emerging roles of miRNAs in age-associated events impacting long-term brain integrity and neurodegenerative disease.