Antibody-drug conjugates (ADCs) are a complex amalgamation of monoclonal antibodies (mAb) and low-molecular-weight toxins. The combination is often a mAb targeted to cancer, delivering a potent cytotoxin to a specific site or cell. The resulting conjugate is complex and typically heterogeneous, making physical chemical characterization challenging. Liquid chromatography coupled with mass spectrometry (LC-MS), and combined with purposefully designed informatics, are powerful tools for the characterization of proteins including mAbs. At Waters we have placed a focus on LC-MS for ADCs based on cysteine, lysine, and engineered conjugates. An ADC-specific LC-MS characterization workflow is illustrated for intact, sub-unit, and peptide levels.