RNA modifications constitute a dynamic and multifaceted layer of post-transcriptional regulation with profound implications for cellular function, development, and disease. Once considered rare curiosities, over 170 distinct RNA modifications are now recognized as integral components of gene expression regulation, affecting processes from splicing and translation to RNA stability and localization. This chapter offers a comprehensive overview of the historical evolution, methodological advancements, and future directions in RNA modification detection. It traces the field’s progress from classical chemical assays through the genomics era to modern direct sequencing and machine learning-driven approaches. Emphasis is placed on the convergence of high-throughput experimental platforms and computational innovations—including deep learning, signal processing, and multi-modal integration—that are transforming epitranscriptomic research. The chapter also explores the biological interpretation of RNA modifications, focusing on positional, structural, and comparative analyses across different biological contexts. Special attention is given to databases and bioinformatic resources essential for cataloging and analyzing modifications. Together, these developments are positioning RNA modification studies as a central component of plant genomics and metagenomics, with promising implications for both basic biology and therapeutic discovery.