Mass spectrometry is one of the best techniques for analyzing the structure of a molecule. It usually provides information about the molecular weight of a substance, and it can present atomic mass units and up to ten thousandths of atomic mass units depending on the accuracy of the mass analyzer. In addition, it provides information on the positive ions formed in the ionization process, which is linked to the chemical structure of the molecule and the nature of the bonds. This technique is widely used for analyzing compounds from natural products. The development of the technique combined with the use of software and databases has been remarkable in recent years, improving the ionization processes and the ion analysis. Since natural products generally constitute a mixture of a complex quantity of components, mechanisms have been developed for coupling to chromatographic techniques of various kinds. This review aims to show how mass spectrometry has contributed to the qualitative quality control in natural products, as well as in the finding of new metabolites of industrial interest.