Differences between Earth’s global mean all-sky outgoing longwave radiation spectrum as observed in 1970 [Interferometric Infrared Spectrometer (IRIS)], 1997 [Interferometric Monitor for Greenhouse Gases (IMG)], and 2012 [Infrared Atmospheric Sounding Instrument (IASI)] are presented. These differences are evaluated to determine whether these are robust signals of multidecadal radiative forcing and hence whether there is the potential for evaluating feedback-type responses. IASI–IRIS differences range from +2 K in the atmospheric window (800–1000 cm−1) to −5.5 K in the 1304 cm−1 CH4 band center. Corresponding IASI–IMG differences are much smaller, at 0.2 and −0.8 K, respectively. More noticeably, IASI–IRIS differences show a distinct step change across the 1042 cm−1 O3 band that is not seen in IASI–IMG comparisons. This step change is a consequence of a difference in behavior when moving from colder to warmer scenes in the IRIS data compared to IASI and IMG. Matched simulations for the relevant periods using ERA reanalyses mimic the spectral behavior shown by IASI and IMG rather than by IRIS. These findings suggest that uncertainties in the spectral response of IRIS preclude the use of these data for quantitative assessments of forcing and feedback processes.