Irradiation-assisted stress-corrosion cracking (IASCC) has been a topic of engineering interest since it was first reported in the 1960s, having been observed in stainless steel cladding on light water reactor fuel elements. This chapter summarizes the results of decades of investigation, showing that IASCC can essentially be defined as the intergranular cracking of austenitic alloys in high-temperature water, where both the material and its environment have been altered by radiation. Of the many interactions that can occur when metals and water are exposed to radiation, the international consensus is that the three with the greatest impact on crack growth rates are the formation of material defects, radiation-induced segregation, and chemical reactions that increase the corrosion potential of water. The chapter discusses each of these in great detail, and includes information on predictive modeling as well.