Abstract: High-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) is a powerful analytical tool which has been applied to a wide variety of studies. One limitation associated with LC-MS/MS analysis is its susceptibility to matrix effect, which should be paid attention. In the present paper, the sources, importance, proposed mechanism, factors, evaluation, eliminating and (or) compensating means of matrix effect in LC-ESI-MS/MS analysis are reviewed, and especially, progress in dealing with matrix effect in typical veterinary drug residues analysis by LC-ESI-MS/MS is summarized.