Ceramides are generally monitored via either their anions or cations formed with electrospray ionization (ESI). While these methods appear adequate for chromatographic assays, they offer limited sensitivity with flow infusion ESI (“shotgun lipidomics”). We therefore evaluated the chloride adducts [M + Cl]− of a number of lipid classes and found 10- to 50-fold increases in assay sensitivity for ceramides, hexosylceramides, lactosylceramides, phytoceramides, dihydroceramides, and ceramide phosphoethanolamines. Chloride adducts of glycerophosphocholines, sphingomyelins, hydroxyl fatty acids, and modified nucleotides also were characterized. Chloride adducts of glycerophosphocholines were particularly useful for the MS/MS analysis of the constituent fatty acids at sn-1 and sn-2.