The increasingly severe problem of esophageal carcinoma on world public health merits the application of new endoscopic methods to assist in early detection and screening. Older methods, such as tissue staining, combined with magnification endoscopy, have shown promising results, while newer techniques capitalize on measurements that discriminate benign from malignant cells based on a wide array of different attributes, ranging from the molecular to the macroscopic level. Instrumentation based on laser-induced fluorescence spectroscopy, ratio fluorescence imaging, elastic scattering spectroscopy, Raman spectroscopy, and optical coherence tomography is presently being tested and compared with standard endoscopic techniques. Using pathologic interpretation of pinch biopsies as the "gold standard," these techniques have shown the ability to identify dysplastic or malignant regions of tissue that would not be visible to the unassisted endoscopist and offer increased sensitivity for detection compared to rigorous random biopsy protocols. The rapid speed of the instruments allows the provision of information to the endoscopist almost instantaneously, potentially allowing therapeutic decisions to be conducted within the confines of the same endoscopic procedure, thereby achieving gains in efficiency and reductions in overall cost. Large, multicenter trials will be necessary to determine the sensitivity and specificity of individual and combined techniques, as well as their ability to favorably influence the early detection, management, and overall outcome of this disease.