Recent advances in quantitative approaches to laser desorption/ionization mass spectrometry (LDI-MS) are selectively reviewed. Numerous efforts have been made to use matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and related techniques for rapid screening and/or monitoring of biological events. Among the various mass ionization spectrometric analysis techniques, MALDI-MS has exceptional potential for high-throughput analysis. Although quantitative analysis with MALDI-MS is challenging, the expansion of its utility is inevitable. It is notable that practical improvement of MALDI-MS can be achieved by preparation of an uniform matrix using binary matrix systems. Broad applications have been established with a self-assembled monolayer for MALDI-MS, referred to as SAMDI-MS. The method could be an essential tool not only for rapid screening but also as a sensitive probe for surface sciences. Complementary to these approaches, labeling of molecules for LDI-MS is introduced as potential tool for the selective detection of specific target molecules.