The patterns of acute-phase response (APR) biomarkers differ upon various inflammatory conditions. Little information is available on the systemic inflammatory response in urticaria/angio-oedema. It has been shown that concentrations of circulating APR biomarkers, IL-6 and C-reactive protein (CRP), are elevated more in severe chronic urticaria (CU) than in patients showing milder urticarial symptoms. It is not clear whether the increase of IL-6 and CRP is merely an epiphenomenon or may contribute to the pathogenesis of CU. It is tempting to speculate that mediators of APR may enhance urticarial inflammation. In addition, there is some association between APR and activation of coagulation/fibrinolysis in CU. It is well known that even slight elevation in CRP baseline concentration is enough to produce significant increase in cardiovascular risk. In this light, one should ask whether CU patients, in particular those showing stronger systemic inflammatory response and long-lasting course are more vulnerable to the cardiovascular events. Apart from highly troublesome symptoms and low quality of life, CU may then involve some remote, serious systemic consequences. Taken together, CU can be identified as a mast cell- and basophil-dependent inflammatory disorder of the skin, which is accompanied by APR. Characterization of APR in CU may appear essential for an insight into the activity of this disease and for assessment of the inflammation degree. Moreover, measurement of these biomarkers might be particularly relevant while assessing CU patients demanding an anti-inflammatory or immunosuppressive therapy. This review summarizes information regarding APR in the course of urticaria/angio-oedema.