Vimentin is known as a cytoskeletal protein that is expressed in mesenchymal and skeletal muscle tissues and plays an important role in the maintenance of the cytoplasmic architecture and cellular integrity. Moreover, vimentin is implicated in various cellular signal transduction pathways involved in cell proliferation and cell migration. Vimentin is highly expressed in lesion sites of various chronic diseases such as fibrosis, cancer, and autoimmune diseases. Vimentin’s high expression in various chronic diseases led to investigate its involvement in pathological mechanisms in chronic diseases. We recently reported that vimentin possesses N-acetyl-D-glucosamine (GlcNAc)-binding activity on cell surfaces. In this review, we describe vimentin’s GlcNAc-binding activity and discuss our hypothesis regarding its physiological relevance.