INTRODUCTION: In recent decades, there has been investigation into the effects of microgravity and microgravity-like environments on cognition and emotion separately. Here we highlight the need of focusing on emotion-cognition interactions as a framework for explaining cognitive performance in space. In particular, by referring to the affective cognition hypothesis, the significant interplay between emotional variables and cognitive processing in space is briefly analyzed. Altogether, this approach shows an interesting pattern of data pointing to a dynamic relation that may be sensitive to microgravity. The importance of examining interactions between emotion and cognition for space performance remains fundamental (e.g., stress-related disorders) and deserves further attention. This approach is ultimately interesting considering the potential effects that microgravity may play on human performance during long-term space missions and on return to Earth.Mammarella N. Towards the affective cognition approach to human performance in space. Aerosp Med Hum Perform. 2020; 91(6):532–534.