Objective: Several reports claim that the enzyme cytochrome c oxidase (CCO) is the primary absorber for red-to-near-infrared (R-NIR) light in cells and causal for mitochondrial adenosine triphosphate (ATP) upregulation, and that pulsed R-NIR light has frequent therapeutic effects, which are superior to those of the continuous wave (CW) mode used in low-level light therapy (LLLT). Background data: Convincing evidence that the absorption of R-NIR photons by CCO is involved in mitochondrial ATP upregulations as well as a coherent explanation for the superiority of the pulsed irradiation mode is presently lacking in the literature. Methods: A comprehensive literature search and rigorous analysis of the data published on the idea that CCO is the primary absorber for R-NIR light, and of the claim that the effectivity of the pulsed irradiation mode can be derived from the absorption of R-NIR photons by CCO, reveal a number of severe inconsistencies. Results: A systematical analysis covering both the theory that CCO is the primary acceptor for R-NIR light and of its use to interpret differences between the biological effect of pulsed light and CW casts doubt on the general validity of the CCO-based hypothesis. Instead, we are offered a simple and conflict-free model accounting for both ATP upregulation and superiority of the pulsed mode in LLLT, which is in agreement with the results of recent laboratory experiments. Conclusions: CCO is not the primary acceptor for R-NIR light.