A shaking table is an experimental facility consisting of a table that loads a structural specimen and actuators that produce acceleration of the table to simulate seismic motions. This is a powerful tool in earthquake engineering because it permits direct observation of the seismic responses of structures under controlled conditions. The 3-D Full-Scale Earthquake Testing Facility, known by its nickname as “E-Defense,” is the largest facility of its kind in terms of table size and operated by National Research Institute for Earth Science and Disaster Resilience (NIED). Since its start of operations in 2005, E-Defense has been contributing to earthquake engineering through as many as 113 experimental projects successfully completed as of fiscal year 2020. To elucidate its future operations as well as to provide other similar facilities with useful knowledge, this paper reviews the E-Defense experiences of operations and research conducted, shares the lessons learned from the experiences, and proposes the future challenges for continued contributions to earthquake engineering, by covering: the history of E-Defense facility operations and its challenges; the contributions of E-Defense to numerical simulation, another important area in earthquake engineering complementing experiment; publications of experimental data and metadata from E-Defense experiments; and international collaborations in experimental research projects.