This article is available online at http://www.jlr.org functions, in addition to structural roles ( 1 ); consequently lipidomic studies have become fundamental for understanding their contribution to health and disease. Mass spectrometry (MS), with its capability of providing structural information, has been the main method of choice in lipidomic studies. Recent technological advances in mass spectrometers, including increased sensitivity, higher mass accuracy, higher scan speeds, and the ability to acquire in both positive and negative mode in one run have resulted in the increased popularity of MS as a detection technique for biomolecules in recent years. This has enabled the mapping of lipids present in fl uids and cells, leading to better understanding of the role of the different lipid classes in the pathophysiology of diseases.A critical step in lipidomic analysis is lipid extraction with an appropriate organic solvent mixture (solvent system) prior to MS detection. The solvent system should be capable of effectively extracting lipids representative of the sample under study without bias, inducing or promoting the degradation of lipids, or introducing contamination by nonlipid components such as sugars, peptides, and amino acids. Therefore, the success in the identifi cation and profi ling of lipids is critically dependent on the efficiency of the extraction step. The performance of the lipid extraction for a given sample (tissue, cell, or fl uid) with a particular solvent system depends on the partitioning of the