Major scientific societies (including the Endocrine Society [16]) as well as public health authorities of various countries are reexamining transsexualism -or, more broadly, gender identity disorder (GID; [1]) -regarding diagnostic categorization, etiology, clinical management, and human rights considerations. In this context, many transgender communities demand the "depathologization" of the condition, i.e., replacing its categorization as a "mental disorder" with the classification as a "neurological," "intersex," or "medical" condition, or even removing it entirely from both DSM-V and ICD-11 [34]. The purpose of this chapter is to examine the evidence supporting the interpretation of GID as an intersex condition.In terms of behavioral or psychological presentation, persons with early-onset GID have much in common with individuals with somatic intersexuality -now subsumed under the category disorder of sex development (DSD; [18]) -who want to change their gender. From early on, they perceive an incongruence between their experienced/expressed gender and their assigned gender and frequently also their sexual anatomy, which may become strong enough to warrant a gender reassignment. However, by definition, individuals with non-DSD GID show no symptoms of somatic intersexuality, and their sex hormone levels appear normal for their assigned gender and age, except for about one-third of natal females with non-DSD GID who have moderately increased androgen levels in the range of hirsute women without genital ambiguity [7,29]. Moreover, findings from studies of peripheral sex steroidrelated nucleotide polymorphisms of steroid receptor or steroid enzyme genes in persons with non-DSD GID [3,4,15,17,33] have been inconsistent or negative.The interpretation of GID as a CNS-limited form of intersexuality would need corroboration by one or more of several lines of evidence, among these (1) genetically based systemic prenatal sex hormone abnormalities that do not markedly affect the reproductive anatomy, but nevertheless influence brain and behavior; (2) abnormal sex hormone levels in the developing brain or respective CNS-limited hormone receptor defects; (3) abnormalities in the genes that interact with sex hormones to bring about the sexual differentiation of the brain; and (4) abnormalities of the neuroanatomic structures that underlie normative sex differences in gendered behavior.While normative sex differences in the neuroanatomy of the human brain are pervasive on diverse structural levels [9,21], the mechanisms of masculinization, feminization, demasculinization, and defeminization of the human brain are not yet well understood. It is clear from extensive research on non-human mammals that both genetic and hormonal factors play a significant role in the sexual differentiation of the brain. For instance, 4,508 genes are actively transcribed in the mouse brain; among these, 257 genes are more highly expressed in males and 355 in females [36]. Most sex-related genes are steroid dependent, but some are independent [10,3...