Electrospray ionization and atmospheric pressure chemical ionization (APCI) have evolved recently as very useful tools for the liquid chromatographic-mass spectrometric (LC-MS) analysis of polar substances. Non-polar compounds, however, are difficult to analyze with these atmospheric pressure ionization techniques due to their soft ionization mechanism. Recently, new approaches have been introduced which are likely to overcome this obstacle, at least partly. On-line electrochemical conversion of the analytes to more polar reaction products, atmospheric pressure photoionization, atmospheric pressure electron capture negativeion-MS and coordination ionspray-MS are four techniques which are presented in detail compared and discussed critically with respect to their current status and future perspectives. Particular focus is directed from a chemical viewpoint on the substance groups which are accessible by each of the new approaches.