Current biological therapies for inflammatory bowel disease reflect the exponential advancement in understanding the human intestinal immune system and particularly the biology of intestinal inflammation over the past decade. The better understanding of the mechanisms of inflammatory bowel disease has evolved from descriptive clinical data and genetically engineered animal models. It led to great interest in a variety of new therapeutic agents and procedures with novel actions. This review will discuss the mechanisms of biologics (antibodies against pro-inflammatory cytokines, T-cell antibodies, anti-inflammatory cytokines, adhesion molecule blockers, growth factors, colony stimulating factors, fusion proteins, antisense oligonucleotides, hormones, immunostimulatory DNA (ISS-DNA, CpG Oligodeoxynucleotides) and parasites (Trichuris suis eggs), used in inflammatory bowel disease and summarize the available data on investigational and approved agents, and briefly touch on probiotics and extracorporeal immunomodulation (leukocyte apheresis and photoapheresis). Based on the data discussed, it appears that biologics may play an increasing role in managing inflammatory bowel disease in the near future.