Small nucleolar RNAs (snoRNAs) are a class of small RNA molecules that play a pivotal role in diverse cellular processes and are extensively implicated in the pathophysiology of various diseases. Here, we provide a comprehensive overview of snoRNAs, encompassing their classification, biogenesis, and both canonical and noncanonical functions. Canonical roles include guiding RNA modifications such as 2'-O-methylation, pseudouridylation, and N4-acetylcytidine modification in targeted RNA molecules, as well as facilitating ribosome biogenesis. Noncanonical roles involve regulating mRNA processing, modulating alternative splicing, generating snoRNA-derived small RNAs, and interacting with long noncoding RNAs. Dysregulation of snoRNAs has been implicated in various human diseases, such as cancer, neurodegenerative disorders, cardiovascular diseases, immunity- and inflammation-related conditions, and aging, highlighting their potential as diagnostic and prognostic biomarkers. Advances in high-throughput sequencing, structural biology, and bioinformatics tools have significantly contributed to the detection, screening, and exploration of the intricate biofunctions of snoRNAs. However, despite these technological advancements, challenges remain in unraveling the biological complexity of snoRNAs and translating these findings into clinical applications. This review discusses the current state of snoRNA research, recent technological breakthroughs, and future directions, emphasizing their emerging roles in health and disease.© 2025 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.