This guide, prepared with the assistance of members of the AMC Mass Spectrometry Sub-Committee, brings together practical advice to assist LC-MS users avoid many common problems and to develop reliable, quantitative applications as quickly and cheaply as possible.  Achieving reliable quantitation by LC-MS depends not only on correct use of the instrumentation but also on correct development and use of the entire analytical method.  Extensive advice on aspects such as sample preparation and calibration strategies is included.  Experience shows that many errors in analytical data result not from lack of understanding of the measurement techniques but as a result of simple and avoidable mistakes during their application.   A brief overview of some common issues is also provided.