Beyond their role in neutralization, antibodies mediate functions such as phagocytosis, cytotoxicity, and maintenance of immune homeostasis. Two modifications to the constant domain control antibody activity: theirreversible genomic selection of isotype/subclass and alterations in glycosylation. Because glycosylation alters the affinity of antibodies for Fc receptors, evidence suggests that glycosylation is a central mechanism for the immune system to tune a broad range of biological activities. While monoclonal therapeutics have exploited glycosylation to improve function, its in vivo control and whether it may be selectively harnessed to target pathogens and/or tumors isunknown. Here, we review the process of antibody glycosylation, how it changes with disease, how it impacts antibody functionality, and the potential for deliberately controlling this biological activity.