Gender is an important factor to consider in understanding the clinical presentation, management, and developmental trajectory of children with neuropsychiatric disorders. While much is known about the clinical and neurobehavioural profiles of boys with neuropsychiatric disorders, surprisingly little is known about girls. The aim of this chapter was to review our understanding of gender by considering the most prevalent childhood onset neuropsychiatric disorders, autism and Fragile X syndrome. This chapter highlights findings which suggest that girls with autism and Fragile X syndrome show some unique differences in cognitive and clinical profiles when compared to boys with these conditions; this may indicate the need for innovative assessment and management approaches which take gender into consideration. Our understanding of how differences emerge in boys and girls with neuropsychiatric disorders is unclear, future research needs to focus on the role of biological maturation rates, sex hormones, and psychosocial factors in order to progress this field.