The applications of liquid chromatography-mass spectrometry (LC-MS) have exploded in innumerable analytical fields, including pesticide-residue determination. There is no doubt that LC-MS is currently competing with gas chromatography (GC)-MS for the status of ‘reference’ analytical technique to determine pesticide residues and that its ever-increasing application is bound to the evolution of modern instruments and their growing performance qualities. We highlight the large number and variety of pesticides that can be readily determined using such instruments, the respective merits of the different mass analyzers, and the improvements brought about by tandem MS (MS 2 ). We also discuss new applications of LC-MS in this field, such as “non-target” screening procedures and unknown identification by MS or MS n presenting the different solutions proposed to solve this challenging problem. Finally, we address the opportunities afforded by the most recent instrument designs.