Physicians rely heavily on the presence of disease markers to support or even at times modify their clinical impression for certain diseases that can only be diagnosed clinically. Typically these markers play an important role in helping to establish a diagnosis and to evaluate the activity of a chronic disease over time. The diagnosis of inflammatory bowel disease (IBD), however, is not based solely on clinical grounds. Invasive endoscopic and radiological as well as histopathological criteria need to be met in order to make a correct diagnosis and differentiate disease subtypes. The search for novel diagnostic approaches that accurately distinguishes a group of patients with IBD from those unaffected by the disease has become a focus in IBD research. This search, however, has taken a very exciting turn in the direction of finding biologic and genetic markers that can assess the natural history and predict the course of individual’s disease including response to treatments over time.