Matrix components in the extract may influence the ionization efficiency of an analyte, and in most cases, suppress the formation of ions. This will deteriorate the sensitivity, accuracy, and precision of the analysis using liquid chromatography/mass spectrometry. Because a mass spectrometer, especially a tandem mass spectrometer, possesses unparalleled sensitivity and selectivity, and many of the matrix components are unseen because of not ionized, the issue of matrix effects is usually overlooked. This article introduces the aspects of matrix effects, the methods for evaluating them, and the solutions to the relating analytical problems.