Contrast agents are increasingly being used to characterize the vasculature in an organ of interest, to better delineate benign from malignant pathology and to aid in staging and directing therapeutic procedures. We review the mechanisms of action of first, second and third generation contrast agents and their use in various endoscopic procedures in the gastrointestinal tract. Various applications of contrast-enhanced endoscopic ultrasonography include differentiating benign from malignant mediastinal lymphadenopathy, assessment of depth of invasion of esophageal, gastric and gall bladder cancers and visualization of the portal venous system and esophageal varices. In addition, contrast agents can be used to differentiate pancreatic lesions. The use of color Doppler further increases the ability to diagnose and differentiate various pancreatic malignancies. The sensitivity of power Doppler sonography to depict tumor neovascularization can be increased by contrast agents. Contrast-enhanced harmonic imaging is a useful aid in identifying the tumor vasculature and studying pancreatic microperfusion. In the future, these techniques could potentially be used to quantify tumor perfusion, to assess and monitor the efficacy of antiangiogenic agents, to assist targeted drug delivery and allow molecular imaging.