Diagnostics of inflammatory bowel diseases (IBDs) currently relies on a combination of biological and morphological tests. The current method of diagnostic remains a critical challenge for physicians in part due to their invasiveness and also for their limitations in term of diagnosis, prognosis, disease activity and severity assessment, and therapeutic outcomes. Laboratory biomarkers can be used in the diagnosis and management of IBD, but none of them has been proven to be ideal. Increasing efforts are being made to discover new biomarkers that can discriminate between the types of IBD, predict future responses to treatment, and aid in differential diagnosis, treatment planning, and prognosis prediction. This review addresses the potential for current biomarkers and the emergence of the concept of biomarker signatures in IBD diagnostic and personalized medicine.