Combined liquid chromatography-mass spectrometry has a long history of promises and breakthroughs. Many interfaces have been developed and commercialized over the past 25 years. Most of these have subsequently disappeared again, because of apparent problems, e.g. moving belt, direct liquid introduction, and thermospray. In the past few years, a real breakthrough has been made and years of promises are redeemed. Interfaces applied in combination with atmospheric-pressure chemical ionization have changed LC-MS, especially with respect to ease of operation, robustness, detection limits, and applicability ranges. LC-MS and related techniques have entered routine laboratories within pharmaceutical industries and related contract research institutes, laboratories concerned with biochemistry, biotechnology, environmental analysis, natural product research, and many other areas. Furthermore, other mass analysers than linear (triple) quadrupole instruments have found extensive use. From this perspective, the editors have invited authors both from fundamental, innovative instrumental and application-oriented research groups to contribute papers to this issue on Current Practice of LC-MS. The result is a clear perspective on the current practice of LC-MS, as well as on new instrumental developments taking place.