Esophageal diseases are highly prevalent and carry significant socioeconomic burden. Despite the apparently simple function of the esophagus, we still struggle to better understand its physiology and pathophysiology. The assessment of large data sets and application of multiscale mathematical organ models have gained attention as part of the Physiome Project. This has long been recognized in cardiology but has only recently gained attention for the gastrointestinal(GI) tract. The term "esophagiome" implies a holistic assessment of esophageal function, from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. These anatomical, mechanical, and physiological models underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease. Functional models incorporate anatomical details with sensory-motor responses, especially related to biomechanical functions such as bolus transport. Our review builds on previous reviews and focuses on assessment of detailed anatomical and geometric data using advanced imaging technology for evaluation of gastro-esophageal reflux disease (GERD), and on esophageal mechanophysiology assessed using technologies that distend the esophagus. Integration of mechanics- and physiology-based analysis is a useful characteristic of the esophagiome. Experimental data on pressures and geometric characteristics are useful for the validation of mathematical and computer models of the esophagus that may provide predictions of novel endoscopic, surgical, and pharmaceutical treatment options.