Neutralizing antibody is fundamental for the effective clearance of many pathogens. In addition, non-neutralizing antibody functions have rapidly gained prominence. The N-glycan structure of antibody can help direct appropriate innate cell effector functions. Thus, dynamic communication between innate and adaptive arms via antibody glycosylation can be crucial for modulating between pro-inflammatory or anti-inflammatory responses. Antibody N-glycan profiles are increasingly used as biomarkers to distinguish between disease states and severity. Emerging evidence suggests that aberrant glycan profiles may impede effective immune responses, but whether they are a consequence or cause of pathology remains unclear. Untangling the role of antibody glycan profiles in pathogenesis and how they are modulated by the microenvironment will expand our ability to assess and modify disease outcomes.