Sex-based differences in immune responses significantly influence susceptibility to infectious and autoimmune diseases. Despite evidence of these differences, research and clinical practice often overlook them, leading to inadequate treatment strategies. X-linked genes, hormones, and societal factors contribute to these disparities. For example, males generally experience more severe infections than females, while females are more prone to autoimmune diseases like systemic lupus erythematosus (SLE), Graves' disease, and multiple sclerosis. Conversely, certain diseases like ankylosing spondylitis are more common in males. Sex-based differences in disease susceptibility are influenced by genetic factors, including X-chromosome inactivation, hormone levels, and anatomical differences. These differences affect pharmacokinetics and pharmacodynamics, leading to variations in drug efficacy and side effects. Historically, women were excluded from clinical trials, resulting in a lack of data on sex-based differences. Recent policies require inclusion of both sexes in clinical trials, but compliance remains low. Estrogen plays a crucial role in immune responses, enhancing cell-mediated and humoral immunity in females. It influences T-cell regulation, B-cell development, and cytokine production. Hormonal fluctuations during the menstrual cycle affect immune responses, with higher estrogen levels promoting T-regulatory cells and reducing inflammation. However, lower estrogen levels are associated with a TH1-polarized response, which can increase inflammation. Androgens, such as testosterone, generally suppress immune function, reducing T- and B-cell proliferation. Estrogen also modulates innate immune responses by reducing pro-inflammatory cytokine production in monocytes and macrophages. These hormonal influences contribute to differences in disease susceptibility and severity between males and females. Sex-based differences in immune responses also affect the progression of viral infections. For example, females may have more robust innate antiviral responses, leading to lower viral loads and reduced disease severity. However, certain infections, like Dengue virus, are more severe in females. These differences highlight the importance of considering sex in clinical trials and drug development. The impact of gender differences on disease susceptibility extends beyond biological factors, influenced by cultural and societal contexts. For instance, women in sub-Saharan Africa are at higher risk of HIV due to social and economic factors. These gender differences underscore the need for comprehensive research that considers both biological and social factors in disease management and treatment.Sex-based differences in immune responses significantly influence susceptibility to infectious and autoimmune diseases. Despite evidence of these differences, research and clinical practice often overlook them, leading to inadequate treatment strategies. X-linked genes, hormones, and societal factors contribute to these disparities. For example, males generally experience more severe infections than females, while females are more prone to autoimmune diseases like systemic lupus erythematosus (SLE), Graves' disease, and multiple sclerosis. Conversely, certain diseases like ankylosing spondylitis are more common in males. Sex-based differences in disease susceptibility are influenced by genetic factors, including X-chromosome inactivation, hormone levels, and anatomical differences. These differences affect pharmacokinetics and pharmacodynamics, leading to variations in drug efficacy and side effects. Historically, women were excluded from clinical trials, resulting in a lack of data on sex-based differences. Recent policies require inclusion of both sexes in clinical trials, but compliance remains low. Estrogen plays a crucial role in immune responses, enhancing cell-mediated and humoral immunity in females. It influences T-cell regulation, B-cell development, and cytokine production. Hormonal fluctuations during the menstrual cycle affect immune responses, with higher estrogen levels promoting T-regulatory cells and reducing inflammation. However, lower estrogen levels are associated with a TH1-polarized response, which can increase inflammation. Androgens, such as testosterone, generally suppress immune function, reducing T- and B-cell proliferation. Estrogen also modulates innate immune responses by reducing pro-inflammatory cytokine production in monocytes and macrophages. These hormonal influences contribute to differences in disease susceptibility and severity between males and females. Sex-based differences in immune responses also affect the progression of viral infections. For example, females may have more robust innate antiviral responses, leading to lower viral loads and reduced disease severity. However, certain infections, like Dengue virus, are more severe in females. These differences highlight the importance of considering sex in clinical trials and drug development. The impact of gender differences on disease susceptibility extends beyond biological factors, influenced by cultural and societal contexts. For instance, women in sub-Saharan Africa are at higher risk of HIV due to social and economic factors. These gender differences underscore the need for comprehensive research that considers both biological and social factors in disease management and treatment.