Abstract: The power of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) in proteomics is well recognized. However, its application for lipidomic analysis has been hampered due to a number of caveats including high matrix background, severe ion suppression, serious post-source decay, and apparent inhomogeneous distribution of lipids at spots¹.Recently, great efforts have been made to address these drawbacks. A number of developments in this area have been made, including new techniques (e.g., TLC-blot-MALDI-MS), new applications (e.g., direct profiling and mapping of lipids from tissues), and new matrices (e.g., 9-aminoacridine (9-AA)). These new developments are outlined in the presentation.The emphasis of this work is on the application of 9-AA on lipidomic analysis as we have recently conducted^2-3. We have found that 9-AA as matrix for MALDI-MS analysis of lipids offers a number of advantages over essentially all other matrices used in the literature, including minimal matrix background, reduced post-source decay, enhanced ionization efficiency (particularly in the negative-ion mode), and increased sensitivity for certain lipid classes (e.g., sulfatide). We have also demonstrated that many classes of lipids can be directly analyzed from a lipid extract of a biological sample and the spectra acquired by MALDI-MS with 9-AA as matrix are comparable with those obtained from electrospray ionization MS which has recently been used as a “golden standard” for quantitative analysis of lipids. Collectively, the recent developments of MALDI-MS provide new sprints for lipidomic research.