The etiopathogenesis of Crohn's disease (CD) and ulcerative Colitis (UC), the two major forms of inflammatory bowel disease (IBD), is still unknown. Although the exact cause and mechanisms of both IBD have yet to be completely understood, it is widely accepted that both CD and UC result from an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. In the last few years a tremendous advance in knowledge of the mechanisms underlying intestinal inflammation in IBD has been achieved, leading to new therapeutic targets and novel drugs. These new therapeutic weapons have been specifically designed to selective shut down intestinal inflammation at different levels. Aim of this review is to summarize the recent advances in IBD pathophysiology and the new therapeutic targets and drugs that are changing the IBD clinical management.