The most widely used ionization techniques in liquid chromatography-mass spectrometry (LC-MS) are electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI). All three provide user friendly coupling of LC to MS. Achieving optimal LC-MS conditions is not always easy, however, owing to the complexity of ionization processes and the many parameters affecting mass spectrometric sensitivity and chromatographic performance. The selection of eluent composition requires particular attention since a solvent that is optimal for analyte ionization often does not provide acceptable retention and resolution in LC. Compromises must then be made between ionization and chromatographic separation efficiencies. The review presents an overview of studies concerning the effect of eluent composition on the ionization efficiency of ESI, APCI and APPI in LC-MS. Solvent characteristics are discussed in the light of ionization theories, and selected analytical applications are described. The aim is to provide practical background information for the development and optimization of LC-MS methods.