The spent fuel rods from nuclear reactors are termed 'High Level Nuclear Waste' (HLW). Once 'burned' in a reactor, the fuel is in the order of a million times more radioactive than when it was loaded. Because direct exposure would deliver a lethal dose within a few seconds, high level waste is handled by remote control.

With high-level waste the main problem is that the continuing spontaneous radioactive decay gives off so much heat that water temperature is raised above the boiling point. Therefore containers with concentrated liquid waste must be constantly cooled.

After a year or two of such forced-cooling the short-lived isotopes decay and the waste, now containing mainly the long-lived isotopes (the chief "remnants" being strontium-90 and cesium-137), can be treated in the same way as medium-level waste. Because both reactors and high-level waste containers require constant cooling (usually by circulating water), the centres of nuclear industry are often located near rivers or large lakes.

Spent fuel rods are sometimes dissolved in nitric acid for plutonium extraction in reprocessing plants. Reprocessing wastes are sometimes included in the category of High Level Waste - as they should be - but are often given their own slightly euphemistic definition of Long-Lived Intermediate Level Wastes (LLILW).