MS as a characterization technique for large, complex structures such as mAbs has advanced greatly in recent years. The flexible nature of the technique has enabled mass spectrometers to be coupled to a series of other alternative analytical techniques such as liquid chromatography systems and ion mobility separation devices, delivering an additional separation and/or characterization dimension to an analysis. With the relatively recent introduction of biosimilar and ADC mAb-based therapeutics into the market, the need for a robust characterization technique has never been stronger, and MS is viewed as the most promising contender. To realize the true potential of MS toward biosimilar candidate characterization, however, comprehensive analysis of originator mAbs needs to be performed, with acceptance criteria implemented, which account for the mammalian cell-induced variability that is inherently present. PTMs such as glycosylation have been shown to be essential for potency and efficacy of many mAb-based therapeutics due to their critical role in effector function cell recruitment. MS currently plays a key role in the identification and quantification of glycosylation, and with the inclusion of HDX and IM platforms, MS is elevated to a position where it is capable of understanding the effects of different glyco- sylation profiles upon conformation and receptor binding as well as the dynamics associated with antigen binding. Due to the recent development of mAb-based therapeutics, such as ADCs, the characterization techniques reported are still in their infancy despite significant advances being made. Undoubtedly MS will continue to offer insight into these complex protein systems, and it is hard to envisage another technique that will rival the high-throughput, high-precision and high-accuracy, and cost-effective advantages that MS has to offer.