CRL has expertise in physics, metallurgy, chemistry, biology, and engineering and hosts unique research facilities.

For example, Bertram Brockhouse, a professor at McMaster University, received the 1994 Nobel Prize in Physics for his pioneering work in neutron spectroscopy while at CRL from 1950 to 1962.

At one point, the Chalk River Laboratories produced about one-third of the world's medical isotopes and half of the North American supply.

Despite the declaration of peaceful use, from 1955 to 1985, Chalk River facilities supplied about 254.2 kilograms (560 lb) of plutonium, in the form of spent reactor fuel, to the U.S. Department of Energy to be used in the production of nuclear weapons.

The first incident occurred on December 12, 1952, when there was a power excursion and partial loss of coolant in the NRX reactor, which resulted in significant damage to the core.

The seal of the reactor vessel was blown up four feet, and 4,500 cubic metres (1,200,000 US gal) of radioactive water were found in the cellar of the building.

This shutdown was extended when AECL, in consultation with the Canadian Nuclear Safety Commission (CNSC), decided to connect seismically-qualified emergency power supplies (EPS) to two of the reactor's cooling pumps (in addition to the AC and DC backup power systems already in place), which had been required as part of its August 2006 operating licence issued by the CNSC.

Prime Minister Stephen Harper criticized the CNSC for this shutdown, which "jeopardized the health and safety of tens of thousands of Canadians", insisting that there was no risk, contrary to the testimony of then-CNSC President & CEO Linda Keen.

[19] In its formal report to the CNSC, filed on December 9, 2008 (when the volume of leakage was determined to meet the requirement for such a report) AECL mentioned that 47 litres (10 imp gal; 12 US gal) of heavy water were released from the reactor, about 10% of which evaporated and the rest contained, but affirmed that the spill was not serious and did not present a threat to public health.

This water was systematically collected, purified in an on-site Waste Treatment Centre, and eventually released to the Ottawa River in accordance with CNSC, Health Canada, and Ministry of the Environment regulations.

In mid-May 2009, the heavy water leak at the base of the NRU reactor vessel, first detected in 2008 (see above), returned at a greater rate and prompted another temporary shutdown until August 2010.

It is then expected that multiple microreactors, each the size of a shipping container, will be built at CNL and transported to remote northern communities where they will replace the existing diesel generator infrastructure, saving some 200 million litres of fuel.