The ability to decode nucleic acids has reshaped biological research and biotechnology, enabling systematic analysis of genome structure, gene regulation, and cellular heterogeneity. This chapter reviews the major technological advances that have driven this transformation. We begin with the historical development of Sanger sequencing and its role in establishing the first genome-scale analyses. We then examine the emergence of next-generation sequencing, highlighting the conceptual innovations—massive parallelization, clonal amplification, and cyclic detection chemistries—that enabled high-throughput, cost-effective sequencing. Building on these foundations, we discuss the shift toward single-cell and spatial transcriptomics, which extend sequencing from bulk measurements to the resolution of individual cells and their tissue contexts. Together, these developments illustrate how sequencing technologies have progressed from early linear workflows to multimodal, high-resolution platforms that now support comprehensive interrogation of biological systems.