The article discusses the complex relationship between sex/gender differences and autism, highlighting the need for a 4-level conceptual framework to better understand and address research questions. The authors review existing literature, identifying key findings and implications across four levels: nosological and diagnostic challenges, sex/gender-independent and sex/gender-dependent characteristics, general models of etiology (liability and threshold), and specific etiological–developmental mechanisms. The first level addresses challenges in defining and diagnosing autism in males and females, noting that current diagnostic criteria may be biased. The second level explores similarities and differences between males and females with autism, emphasizing the need for more nuanced approaches. The third level examines general models of etiology, including the multi-factorial multi-threshold model and the multi-factorial sex/gender-differential liability model, which suggest that females may have a greater genetic etiological load and that sex/gender differences in liability distribution may explain the male bias in autism prevalence. The fourth level focuses on specific etiological–developmental mechanisms, including genetic and epigenetic factors, prenatal hormonal environments, and socio-cultural influences. The authors emphasize the importance of considering sex/gender differences in research and clinical practice, as well as the need for more balanced and comprehensive studies. They suggest that future research should focus on clarifying the role of sex/gender in autism etiology and development, and on developing more accurate diagnostic tools and interventions. The article concludes that a better understanding of sex/gender differences in autism is essential for improving diagnosis, treatment, and support for individuals with autism.The article discusses the complex relationship between sex/gender differences and autism, highlighting the need for a 4-level conceptual framework to better understand and address research questions. The authors review existing literature, identifying key findings and implications across four levels: nosological and diagnostic challenges, sex/gender-independent and sex/gender-dependent characteristics, general models of etiology (liability and threshold), and specific etiological–developmental mechanisms. The first level addresses challenges in defining and diagnosing autism in males and females, noting that current diagnostic criteria may be biased. The second level explores similarities and differences between males and females with autism, emphasizing the need for more nuanced approaches. The third level examines general models of etiology, including the multi-factorial multi-threshold model and the multi-factorial sex/gender-differential liability model, which suggest that females may have a greater genetic etiological load and that sex/gender differences in liability distribution may explain the male bias in autism prevalence. The fourth level focuses on specific etiological–developmental mechanisms, including genetic and epigenetic factors, prenatal hormonal environments, and socio-cultural influences. The authors emphasize the importance of considering sex/gender differences in research and clinical practice, as well as the need for more balanced and comprehensive studies. They suggest that future research should focus on clarifying the role of sex/gender in autism etiology and development, and on developing more accurate diagnostic tools and interventions. The article concludes that a better understanding of sex/gender differences in autism is essential for improving diagnosis, treatment, and support for individuals with autism.