This review discusses how crude extracts of selected plants are subjected to column chromatography and the resulting fractions tested for their antibacterial activity towards organisms (e.g., methicillin-resistant-Staphylococcus aureus). We discuss the bioactive column-chromatography fractions being further separated by preparative thin-layer chromatography and the resulting bands being investigated by high-performance liquid chromatography-electrospray ionization-ion trap mass spectrometry (LC-ESI-MS) and ESI-MSn. We then show how the resulting retention times, molecular masses, their fragmentation patterns, the Chemnet database and an in-house quinoline database are used in the dereplication process by structural elucidation of some of the compounds when compared with known structures of natural origin. Some molecular masses and the corresponding fragmentations do not correlate with any known compounds, thus revealing potentially novel natural products that could be investigated on a larger scale and could ultimately find application as new drugs against MRSA and other multi-drug-resistant microorganisms. (C) 2012 Elsevier Ltd. All rights reserved.