In healthy joints, Synovial Fibroblasts (SFs) provide the required stromal support, but are recognized to adopt a pathological role in rheumatoid arthritis, delivering region-specific signals to infiltrating cells that perpetuate inflammation. Interventions targeting SFs would improve current systemic therapies by directly modifying disease progression. Unfortunately, our collective understanding of stromal immunology has not been translated to the clinic and new strategies are needed to find novel therapeutic targets. The vast, and yet unexploited amount of information contained in cell glycomes could offer such molecular targets, as glycans – or carbohydrates – are being increasingly recognized as fundamental regulators of cellular interactions between stromal and immune cells. Our results show that transformation of SFs into pro-inflammatory cells in arthritis is associated with glycan remodelling in response to pro-inflammatory mediators, a process that involves regulation of terminal sialylation. Implications for changes in glycosylation pathways in disease progression and remission will be discussed.