This paper addresses small targets and signal processing from the perspective of rejecting radiation noise spikes. Nuclear and space radiation create noise spikes inside infrared detectors causing an overwhelming number of false alarms, if steps are not taken to mitigate the radiation noise spikes. Traditional radiation device/circuit hardening methods are effective, but must be reapplied to each new technology forcing special design point solutions and parts that are increasingly economically nonviable. Real-time noise mitigation algorithms represent a general hardening solution and have been demonstrated for both Interceptor Seeker and Space Surveillance sensor applications. A new combined HWIL/radiation synthetic test environment has been developed that enables real-time algorithm evaluation over the total system performance envelope, under flight motion simulation and fully dynamic optical sensor scene stimulation. This work was sponsored by the Defense Special Weapons Agency.