Lipids remain one of the most enigmatic classes of biological molecules. Whereas lipids are well known to form basic units of membrane structure and energy storage, deciphering the exact roles and biological interactions of distinct lipid species has proven elusive. How these building blocks are synthesized, trafficked, and stored are also questions that require closer inspection. This tutorial review covers recent advances on the preparation, derivatization, and analysis of lipids. In particular, we describe several chemical approaches that form part of a powerful toolbox for controlling and characterizing lipid structure. We believe these tools will be helpful in numerous applications, including the study of lipid-protein interactions and the development of novel drug delivery systems.