There is an increasing interest in the discovery of new inflammatory bowel disease (IBD) biomarkers able to predict the future patterns of disease and to help in diagnosis, treatment, and prognosis. A biomarker is a substance that can be measured biologically and is associated with an increased risk of the disease. Biomarkers can be a genetic testing factor or proteins in biological samples such as serum, plasma, and cellular subpopulations. All of them should be studied to find out their utility in the management of IBD. Ulcerative colitis and Crohn's disease are relapsing and remitting chronic IBDs characterized by a global immune defect. The gold standard of their diagnosis is histological evaluation performed during endoscopic procedures. Several studies have focused on the identification and combination of less invasive diagnostic serum biomarkers. Nowadays, diagnostic serum tests are not able either to determine whether and when the relapse will occur once the disease is in remission state or to select a patient phenotype more responsive to a specific therapy and more susceptible to different types of complication. In this review we analyze and report the current understanding in IBD biomarkers and discuss potential future biomarkers and new developments of proteomics, such as subproteomics, as an innovative approach for the classification of patients according to their pattern of protein expression.