The One-Bead One-Compound (OBOC) technology, developed early in my career, has revolutionized combinatorial chemistry and drug discovery. Originating from my work on idiotype-specific peptides, OBOC enables high-throughput screening of diverse libraries on individual beads. Over decades, advancements in decoding, screening, and encoding have expanded its applications to therapeutics, nanomedicine, and functional genomics. This chapter reflects on OBOC’s origins, impact, and future potential in biomedical research.