Neural circuitry involved in anxiety and fear-related disorders exhibits strong sexual modulation. A limited number of studies integrating female and male data have revealed differences in neural networks, and distinct interconnectivity between these brain areas. Despite the efforts to incorporate female or mixed-sex data, there is compelling evidence that sex, as a biological variable, significantly influences fear processing. This chapter presents primary findings on sex differences in fear circuitry. It is imperative to consider this factor to ensure scientific research’s integrity and understand how fear is processed in the central nervous system.