Pathologic complete response after neoadjuvant chemoradiation therapy is associated with increased survival in esophageal cancer. Early detection of response or nonresponse to neoadjuvant chemoradiation might allow individualization of treatment strategies and avoidance of unnecessary treatment. Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) permits detection of changes in tumor proliferation before any change in tumor size occurs, and FDG-PET findings have been correlated with outcomes in esophageal cancer. However, FDG-PET may fail to distinguish between residual tumor and inflammation and between complete response and partial response with substantial residual tumor burden. PET with the nucleoside analogue 3'-deoxy-3'-18F-fluorothymidine (FLT) has been found to be more accurate than FDG-PET in visualizing early changes in tumor proliferation. In a recent study in experimental models of esophageal cancer, FLT-PET was more accurate than FDG-PET in detecting early changes in proliferation following docetaxel and radiation therapy in human SEG-1 cells and mouse SEG-1 xenografts, including having a much stronger correlation with histologic findings. Clinical studies are needed to determine if FLT-PET can distinguish among degrees of response to neoadjuvant chemoradiation in patients with esophageal cancer.