Mass spectrometry of intact synthetic polymers has been limited to field desorption (FD) MS for many years. More recently, soft ionization techniques such as electrospray (ESI) and matrix-assisted laser desorption/ionization (MALDI) and the revival of time-of-flight analyzers created new opportunities for the characterization of polymers. In this review emphasis is put on MALDI time-of-flight mass spectrometry of polymers. The selection of an appropriate MALDI matrix, cationization salt and sample preparation techniques are critical success factors for obtaining a reliable mass spectrum and to infer structural information such as monomer mass(es) and end-groups. However even under optimized conditions mass discrimination in the analysis of polydisperse polymers and specific oligomer discrimination might occur. Hence hyphenated techniques such as size exclusion chromatography (SEC)/MALDI have been developed. Many different polymer applications appeared in recent literature, but most studies deal with homopolymers. Many challenges remain, particularly in the fields of halogenated polymers, polyolefines, copolymers, blends, and in the sequencing of block-copolymers. © 1999 John Wiley & Sons, Inc., Mass Spec Rev 18: 309–344, 1999