Lipids are highly dynamic molecules with many different roles ranging from structural to signaling. Alterations in particular lipid levels change cellular behavior. In humans, inappropriate changes may manifest as diseases such as Alzheimer’s, atherosclerosis, diabetes, obesity, and even cancer. This has led to a great interest in monitoring lipid changes both during normal cellular processes and in disease situations. With the advent of rapid mass spectrometry, it has become possible to analyze many lipids within a single sample with unsurpassed sensitivity and detail. Coupling this with liquid chromatography potentially enables the complete profiling of all the phospholipids, both major and minor, from a single sample within a single analysis run.