Gender dysphoria (GD) is the distress a person experiences due to inconsistency between their gender identity—their personal sense of their own gender—and their sex assigned at birth. The term replaced the previous diagnostic label of gender identity disorder (GID) in 2013 with the release of the diagnostic manual DSM-5. The condition was renamed to remove the stigma associated with the term disorder. The ICD-11, which does not consider it a mental disorder, uses the term gender incongruence (GI) instead of gender dysphoria, defined as a marked and persistent mismatch between gender identity and assigned sex, regardless of distress or impairment.

Not all transgender people have gender dysphoria. Gender nonconformity is not the same thing as gender dysphoria and does not always lead to dysphoria or distress. In pre-pubertal youth, the diagnoses are gender dysphoria in childhood and gender incongruence of childhood. The causes of gender incongruence are unknown but a gender identity likely reflects genetic, biological, environmental, and cultural factors.

Diagnosis can be given at any age, although gender dysphoria in children and adolescents may manifest differently than in adults. Complications may include anxiety, depression, and eating disorders. Treatment for gender dysphoria includes social transitioning and often includes hormone replacement therapy (HRT) or gender-affirming surgeries, and psychotherapy.

Some researchers and transgender people argue for the declassification of the condition because they say the diagnosis pathologizes gender variance and reinforces the binary model of gender. However, this declassification could carry implications for healthcare accessibility, as HRT and gender-affirming surgery could be deemed cosmetic by insurance providers, as opposed to medically necessary treatment, thereby affecting coverage.

In the DSM-5, a marked incongruence between a person's felt gender and assigned sex or gender (usually at birth) is the core component of the diagnosis, which requires distress about the incongruence. In pre-pubertal youth it may manifest as an insistence that they are, or will grow up to be, another gender than the one assigned at birth, an aversion to their assigned gender, or an insistence they have or desire to have different genitalia. They may express aversions to stereotypically gendered activities and desire opposite sex-typical toys, games, activities, or playmates though this may be less prominent in surroundings with fewer stereotypes.

The DSM-5 states that gender dysphoria tends to be early-onset (starting prior to puberty) or late-onset (starting during or after puberty) in non-intersex individuals. Those with early-onset GD which continues into adolescence mostly identify as heterosexual, being attracted to their assigned gender at birth. In some cases, the GD desists or is denied, during which the youth may identify as lesbian or gay, though some may experience a later resurgence in GD. Some of those with late-onset GD report desire to transition during childhood that was not verbalized and others have no recollections of childhood gender dysphoria. According to the American Psychiatric Association, those who experience gender dysphoria later in life "often report having secretly hidden their gender dysphoric feelings from others when they were younger". No particular sexual orientation indicates gender dysphoria. A 2021 review in Dialogues in Clinical Neuroscience found no relation to sexual orientation, but acknowledged that historically the two were often erroneously conflated. The British National Health Service also stated "gender dysphoria is not related to sexual orientation".

In a 2020 position statement, the Endocrine Society stated that in the late 20th century, transgender and gender incongruent people were thought to suffer a mental health disorder and gender identity was considered malleable and subject to external influences. But that this was no longer considered valid as "Considerable scientific evidence has emerged demonstrating a durable biological element underlying gender identity. Individuals may make choices due to other factors in their lives, but there do not seem to be external forces that genuinely cause individuals to change gender identity".

The cited evidence includes that attempts to change the gender identity of intersex patients to match their genitalia or chromosomes are generally unsuccessful, that there is evidence that higher levels of exposure to androgens in utero causes higher rates of male gender identity among those with female chromosomes, that those with complete androgen insensitivity syndrome among those with male chromosomes typically have a female gender identity, that identical twins are more likely to both be transgender than non-identical twins, and that brain scans have shown associations with gender identity rather than genitalia or chromosomes.