Treatment planning for ulcerative colitis (UC) is based on disease severity and exact diagnosis, the latter of which is currently achieved through assessments of clinical presentation and typical endoscopic appearance coupled with histological confirmation [1–3]. In clinical practice, however, the role of repeated endoscopic examination is often limited because of its expense and invasiveness. Moreover, there is no single gold-standard test, pathogenomic symptom, or sign that can be used to definitively diagnose or determine the severity of UC. Instead, many criteria and indices for UC severity have been developed to assess the disease activity of UC [4–6]. However, the factors included in such indices are generally subjective. An ideal test for UC should be non-invasive, easily performed, and provide objective, reproducible, sensitive, and specific results in order to rapidly assess the disease status of patients as well as predict treatment outcomes. Various biological markers, which can be assessed objectively and non-invasively, may be useful alternatives to current methods for diagnosing or assessing the severity of UC. Here, we review the advantages and limitations of several leading biological markers for UC including acute phase reactions and fecal markers (Tables 1–3).