Technical Abstract: The low affinity of Rubisco for CO2 and its dual nature as an oxygenase limit the possible increase in net photosynthesis with temperature. For cotton, comparisons of measured rates of net photosynthesis with predicted rates indicate that direct inhibition of photosynthesis occurs at temperatures higher than about 30ºC. Inhibition of photosynthesis by moderate heat stress (i.e., 30 to 42ºC) is generally attributed to reduced rates of RuBP regeneration caused by disruption of electron transport activity. However, measurements of chlorophyll fluorescence and metabolite levels at air-levels of CO2 indicate that electron transport activity is not limiting at temperatures that inhibit CO2 fixation. Instead, recent evidence shows that inhibition of net photosynthesis correlates with a decrease in the activation state of Rubisco in both C3 and C4 plants and that this decrease in the amount of active Rubisco can fully account for the temperature response of net photosynthesis. Biochemically, the decrease in Rubisco activation can be attributed to 1) more rapid deactivation of Rubisco caused by a faster rate of dead-end product formation and 2) slower reactivation of Rubisco by activase. The net result is that as temperature increases activase becomes less effective in keeping Rubisco activated. In this opinionated review, we discuss how these processes provide a mechanism for the inhibition of photosynthesis by moderate heat stress.