Asthma is a heterogenous disease, and its prevalence and severity are different in malesversusfemales through various ages. As children, boys have an increased prevalence of asthma. As adults, women have an increased prevalence and severity of asthma. Sex hormones, genetic and epigenetic variations, social and environmental factors, and responses to asthma therapeutics are important factors in the sex differences observed in asthma incidence, prevalence and severity. For women, fluctuations in sex hormone levels during puberty, the menstrual cycle and pregnancy are associated with asthma pathogenesis. Further, sex differences in gene expression and epigenetic modifications and responses to environmental factors, including SARS-CoV-2 infections, are associated with differences in asthma incidence, prevalence and symptoms. We review the role of sex hormones, genetics and epigenetics, and their interactions with the environment in the clinical manifestations and therapeutic response of asthma.