The incidence of esophageal cancer in the United States has been increasing in recent years. Since multimodality therapy for esophageal cancer has produced discouraging results, recent approaches have focused on molecular biological techniques, positron emission tomography, and minimally invasive surgery to improve pretreatment staging which will facilitate a more accurate assessment of new treatment. This article summarizes the results of studies investigating these approaches and outlines the strategy currently used at the University of Pittsburgh Medical Center.