There are several challenges to the application of thorium as a nuclear fuel, particularly for solid fuel reactors:
In contrast to uranium, naturally occurring thorium is effectively mononuclidic and contains no fissile isotopes; fissile material, generally ,  or plutonium, must be added to achieve criticality. This, along with the high sintering temperature necessary to make thorium-dioxide fuel, complicates fuel fabrication. Oak Ridge National Laboratory experimented with thorium tetrafluoride as fuel in a molten salt reactor from 1964 to 1969, which was expected to be easier to process and separate from contaminants that slow or stop the chain reaction.
In an open fuel cycle (i.e. utilizing  in situ), higher burnup is necessary to achieve a favorable neutron economy. Although thorium dioxide performed well at burnups of 170,000 MWd/t and 150,000 MWd/t at Fort St. Vrain Generating Station and AVR respectively, challenges complicate achieving this in light water reactors (LWR), which compose the vast majority of existing power reactors.
In a once-through thorium fuel cycle, thorium-based fuels produce far less long-lived transuranics than uranium-based fuels,
some long-lived actinide products constitute a long-term radiological impact, especially  and . On a closed cycle, and  can be reprocessed.  is also considered an excellent burnable poison absorber in light water reactors.
Another challenge associated with the thorium fuel cycle is the comparatively long interval over which  breeds to . The half-life of  is about 27 days, which is an order of magnitude longer than the half-life of . As a result, substantial  develops in thorium-based fuels.  is a significant neutron absorber and, although it eventually breeds into fissile , this requires two more neutron absorptions, which degrades neutron economy and increases the likelihood of transuranic production.
Alternatively, if solid thorium is used in a closed fuel cycle in which  is recycled, remote handling is necessary for fuel fabrication because of the high radiation levels resulting from the decay products of . This is also true of recycled thorium because of the presence of , which is part of the  decay sequence. Further, unlike proven uranium fuel recycling technology (e.g. PUREX), recycling technology for thorium (e.g. THOREX) is only under development.
Although the presence of  complicates matters, there are public documents showing that  has been used once in a nuclear weapon test. The United States tested a composite -plutonium bomb core in the MET (Military Effects Test) blast during Operation Teapot in 1955, though with much lower yield than expected.
Advocates for liquid core and molten salt reactors such as LFTRs claim that these technologies negate thorium's disadvantages present in solid fuelled reactors. As only two liquid-core fluoride salt reactors have been built (the ORNL ARE and MSRE) and neither have used thorium, it is hard to validate the exact benefits.