Immunotherapies are a hot topic, with the potential to impact our understanding of the immune system and treat a diverse array of conditions. Therapeutic monoclonal antibodies (mAbs) are part of this revolution, and clinical chemists are aware of the success of the biologic drugs. Antibodies are not just immunoassay reagents anymore but are also present in clinical serum samples from more and more patients each day. The clinical laboratory will have many roles as mAb therapies expand, including the development of new assays to differentiate a mAb from an endogenous, disease-causing clone and monitoring therapeutic drugs for better patient outcomes and assessing for the loss of response to therapy.Therapeutic mAbs use has expanded significantly in the last 5 years, and depending on their target or their concentration, they may impact routine clinical testing for patients. Optimizing therapy during the induction phase to keep the mAb concentrations above certain thresholds has proven to be associated with improved responses and better outcomes in chronic conditions such as inflammatory bowel disease. This chapter will describe a LC-MS/MS protocol for analysis of tryptic peptides unique to infliximab (clonotypic peptides) for quantitation of the mAb. The protocol can be adapted to other mAbs with similar outcomes and is a useful, relatively simple strategy for measurement of mAbs.