Electrospray ionization-mass spectrometry (ESI-MS) is a powerful technique for the detection, identification, and quantification of organic compounds. As mass spectrometers have become more user-friendly and affordable, many students--often with little experience in mass spectrometry--find themselves needing to incorporate mass spectrometry into their research. Herein, a hands-on laboratory experiment for upper-level undergraduate and graduate students to investigate ESI-MS is described. This experiment provides students with the opportunity to observe and use instrumentation discussed in class, to investigate various modes of operation, to compare triple-stage quadrupole (TSQ) with quadrupole linear ion trap (QLIT) instrumentation, and to decide upon the optimum approach for incorporation of mass spectrometry into their research.