A wide variety of biologic events and mechanisms appear to have roles in the development and progression of Barrett's esophagus-associated neoplastic lesions. Figure 5 is a schematic depiction of these events. This is known as an infernogram (named after Dante's Inferno) (S. Kern, unpublished presentations, 1996). Events at the bottom rings of the inferno are high-frequency mutations; nearer to the top of the inferno are the less common events. The next several years promise many further discoveries of not only high-frequency and low-frequency events, but also their application. Some of the molecular alterations already studied show promise as markers for early cancer detection or prognostication. Eventually, applications of these discoveries should yield new and more effective means of preventing and treating the deadly complications of this troublesome premalignant condition.