Metabolic labeling, in which substrate analogs containing diminutive tags can infiltrate biosynthetic pathways and generate labeled products in cells, has led to dramatic advancements in the means by which complex biomolecules can be detected and biological processes can be elucidated. Within this realm, metabolic labeling of lipid products, particularly in a manner that is headgroup-specific, brings about a number of technical challenges including the complexity of lipid metabolic pathways as well as the simplicity of biosynthetic precursors to headgroup functionality. As such, only a handful of strategies for metabolic labeling of lipids have thus far been reported. However, these approaches provide enticing examples of how strategic modifications to substrate structures, particularly by introducing clickable moieties, can enable the hijacking of lipid biosynthesis. Furthermore, early work in this field has led to an explosion in diverse applications by which these techniques have been exploited to answer key biological questions or detect and track various lipid-containing biological entities. In this article, we review these efforts and emphasize recent advancements in the development and application of lipid metabolic labeling strategies. Copyright © 2020. Published by Elsevier B.V.