Lipids are the most chemically diverse class of biomolecules, comprising over 100k distinct molecular species. Despite their central roles in cellular organization, signaling, and metabolism, they remain among the least understood molecules in living systems. Progress in lipid biology has been constrained by a lack of tools to precisely edit, screen, and visualize lipids in living systems. In this lecture, I will discuss how chemical biology approaches can fill this critical gap by enabling lipidome modulation and functionalization with unprecedented resolution, providing new insights into lipid function.