The soluble urokinase plasminogen activator receptor (suPAR) is the bioactive form of uPAR, a membrane-bound glycoprotein, and it is primarily expressed on the surface of immunologically active cells. Mirroring local inflammation and immune activation, suPAR has gained interest as a potential prognostic biomarker in several inflammatory diseases. Indeed, in many diseases, including cancer, diabetes, cardiovascular diseases, kidney diseases, and inflammatory disorders, higher suPAR concentrations have been associated with disease severity, disease relapse, and mortality. Our review describes and discusses the supporting literature concerning the promising role of suPAR as a biomarker in different autoimmune rheumatic and non-rheumatic diseases.