In 1965, the Atomic Energy Commission, at the advice of the Advisory Committee on Reactor Safeguards, initiated the process that resulted in the establishment of the Heavy Section Steel Technology (HSST) program at Oak Ridge National Laboratory. In 1989, the Heavy-Section Steel Irradiation (HSSI) program, formerly the HSST task on irradiation effects, was formed as a separate program, and in 2007, the HSST/HSSI programs, sponsored by the U.S. Nuclear Regulatory Commission (USNRC), celebrated 40 years of continuous research oriented toward the safety of light-water nuclear reactor pressure vessels (RPVs). This paper presents a summary of results from those programs with a view to future activities. The HSST program was established in 1967 and initially included extensive investigations of heavy-section low-alloy steel plates, forgings, and welds, including metallurgical studies, mechanical properties, fracture toughness (quasi-static and dynamic), fatigue crack-growth, and crack-arrest toughness. Also included were irradiation effects studies, thermal shock analyses, testing of thick-section tensile and fracture specimens, and nondestructive testing. In the subsequent decades, the HSST Program conducted extensive large-scale experiments with intermediate-size vessels (with varying size flaws) pressurized to failure, similar experiments under conditions of thermal shock and even pressurized thermal shock (PTS), wide-plate crack-arrest tests, and biaxial tests with cruciform-shaped specimens. Extensive analytical and numerical studies accompanied these experiments, including the development of computer codes such as the recent Fracture Analysis of Vessels Oak Ridge code currently being used for PTS evaluations. In the absence of radiation damage to the RPVs, fracture of the vessel is improbable. However, it was recognized that exposure to high energy neutrons can result in embrittlement of radiation-sensitive RPV materials. The HSSI Program conducted a series of experiments to assess the effects of neutron irradiation on RPV material behavior, especially fracture toughness. These studies included RPV plates and welds, varying chemical compositions, and fracture toughness specimens up to 101.6 mm (4 in.) thickness. The results of these investigations, in conjunction with results from commercial reactor surveillance programs, are used to develop a methodology for the prediction of radiation effects on RPV materials. Results from the HSST and HSSI programs are used by the USNRC in the evaluation of RPV integrity and regulation of overall nuclear plant safety.