This lecture covers fundamental tools and concepts in Chemical Biology, focusing on interrogating the genome and DNA of living systems. Topics include the central dogma of DNA to RNA to protein, cell cycle phases, nucleosides vs. nucleotides, and representative chemical biology toolsets for probing cellular RNA/DNA. The lecture also delves into the iPOND method for isolating proteins on nascent DNA and pulse-chase analysis. An interlude on the Nobel Prize-winning click chemistry and bioorthogonal chemistry is included, showcasing the impact of these techniques in various fields.