Despite the obvious sex differences in many of the most common neuropsychiatric and neurodegenerative disorders, males and females are still often treated the same from a clinical perspective. Why is that? The simple answer is that there is still too little known about this very complex matter. Sex hormone signaling, genetic sex, sex-biased comorbidities, and social gender perceptions all interact, making discrimination between the impacts of each of these factors hard to evaluate. Adding to the complexity is that important species differences must be taken into account when interpreting data from animal models. Clearly, to overcome this, larger efforts are needed that incorporate epidemiological, experimental, and clinical data to provide a solid scientific base for more personalized and informed clinical decisions that will benefit both men and women suffering from neurological disorders.