Technological innovations have transformed the way scientists approach biological and clinical questions, transiting from conventional ensemble assays in bulk to emphasize on the measurements of single molecules in single cells. In the recent years, single-cell lipidomics is taking on from other omics in adding another dimension of lipid-centric information in individual cells. In this review, we summarize the current technological progress and bottlenecks in single-cell lipidomics, and discuss the unique technical challenges in analyzing lipids within single cells, with particular focus on the importance of accurate lipid identification and quantification. We conclude the review with examples on the potential applications of single-cell lipidomics in biology and clinical medicine - in the construction of cell lineage trees, understanding the heterogeneity of tumor and dissecting host immune responses to various diseases.