Males and females are physiologically distinct in their responses to various anesthetic agents. The brain and central nervous system (CNS), the main target of anesthesia, are sexually dimorphic from birth and continue to differentiate throughout life. Accordingly, gender has a substantial impact on the influence of various anesthetic agents in the brain and CNS. Given the vast differences in the male and female CNS, it is surprising to find that females are often excluded from basic and clinical research studies of anesthesia. In animal research, males are typically studied to avoid the complication of breeding, pregnancy, and hormonal changes in females. In clinical studies, females are also excluded for the variations that occur in the reproductive cycle. Being that approximately half of the surgical population is female, the exclusion of females in anesthesia-related research studies leaves a huge knowledge gap in the literature. In this review, we examine the reported sex-specific differences in the central nervous system's response to anesthesia. Furthermore, we suggest that anesthesia researchers perform experiments on both sexes to further evaluate such differences. We believe a key goal of research studying the interaction of the brain and anesthesia should include the search for knowledge of sex-specific mechanisms that will improve anesthetic care and management in both sexes.