Medical pioneers such as Magnus Hirschfeld and Harry Benjamin made valuable contributions to the field of transsexual care. But perhaps the most important advance—changing the paternalistic attitudes of the medical profession—was spurred by transgender activists themselves.

While cases have been reported throughout history of males feminized by means of castration, sex-reassignment surgery did not come about until the 20th century. The first complete male-to-female operations were performed in Germany in the early 1930s on patients referred by pioneering sexologist Magnus Hirschfeld (whose writings mention incomplete attempts dating back to 1912). Himself a homosexual, Hirschfeld was an early advocate for gay rights and was among the first to study transsexualism—a word he is thought to have coined. He often visited bars in Berlin catering to gays and transvestites as he researched the first-ever book on transgenderism, Die Transvestiten (1910).

The first surgical sex change is variously attributed to two individuals who underwent the procedure in 1930 and 1931. Lili Elbe, formerly Danish painter Einar Wegener, had a series of operations that included the implantation of ovaries. Having undergone castration years earlier, a patient called Dorchen (born Rudolf Richter) received what is likely the first vaginoplasty, performed by Felix Abraham in Berlin. Some female-to-male transsexuals, like Alan Hart in 1918, also sought surgeries—such as ovary removal and mastectomy— to make their bodies better match their identities.

The first sex-reassignment operation to enter the public spotlight in America was that of Christine Jorgensen. The New York Daily News broke the story in December 1952 with the headline "Ex-GI Becomes Blond Bombshell." Tall and attractive, Jorgensen became a popular nightclub performer. "Now, looking back, I realize it was the beginning of the Sexual Revolution," Jorgensen told an interviewer in 1986. "I just happened to be one of the trigger mechanisms."

Harry Benjamin, a German-born doctor who practiced in New York City, traveled frequently to visit Europe’s pre-eminent sexologists. In addition to Hirschfeld—whom Benjamin had met as a university student—he also visited renowned Austrian endocrinologist Eugen Steinach, who conducted some of the first experiments to change the sexual characteristics of animals by castration or implanting testicles. Benjamin later became acquainted with sex researcher Alfred Kinsey, who is thought to have sparked Benjamin’s interest in transsexualism by introducing him to a patient who claimed to be a man trapped in a woman’s body.

Rejecting the prevailing view that transsexuals were either mentally ill or poorly adjusted homosexuals, Benjamin provided sympathetic care to hundreds of patients at his offices in New York and San Francisco in the 1950s. As the publicity surrounding Jorgensen’s sex change gave transgender people new hope, Benjamin’s practice exploded. He became known as the country’s foremost expert on transsexualism, a distinction furthered by the publication of his groundbreaking 1966 book, The Transsexual Phenomenon.

By the late 1950s, the care of transsexuals had improved markedly thanks to medical advances such as skin flap surgery (which reduced the need for disfiguring skin grafts) and hormone therapy. At that time, French plastic surgeon Georges Burou developed the modern penile-inversion technique. Female-to-male techniques improved as well, but creating a fully functional penis remained a surgical challenge. Despite these advances, few U.S. hospitals permitted sex-reassignment surgeries until the following decade.

In the 1960s, the prestigious Johns Hopkins Medical Center set up a gender clinic, which began performing sex-reassignment surgeries in 1966. Some 40 or so university-affiliated gender clinics were established in the ensuing decade, including one at Stanford University in 1969. That same year, Stanley Biber, previously a general surgeon, began performing sex-reassignment operations in Trinidad, Colo., following hand-drawn sketches obtained from Johns Hopkins. Biber went on to become one of the most prominent surgeons in the field, performing 150 operations per year at the height of his career.

In the wake of a 1979 study claiming that male-to-female transsexuals who received sex-reassignment surgery experienced "no objective improvement," gender clinics began to close—led by Johns Hopkins—until only a few remained. To avoid the poor outcomes the study revealed, a group of psychologists, physicians, and other experts created the Harry Benjamin International Gender Dysphoria Association (HBIGDA) and put together a standard of care meant to ensure that only appropriate candidates could obtain sex-reassignment surgery.

Among the characteristics of a supposed good candidate was adherence to a traditional, heterosexual feminine or masculine role. According to the standards (which are still used today), a candidate must first undergo psychotherapy for at least three months. With approval from a psychologist, he or she can obtain a prescription for hormones, then complete the "Real-Life Experience" test, which requires living full-time as the desired gender.

While many transsexuals lauded the HBIGDA standards, subsequent social and political shifts led to controversy. Some transgender people felt they should not have to jump through hoops to receive medical treatment, while others opposed the traditional gender role requirement. In response to such criticism, the latest revision of the standards (2001) relaxed these restrictions. In addition, an alternative standard of care was put forth by the International Conference on Transgender Law and Employment Policy in 1993, stating, "Persons have the right to express their gender identity through changes to their physical appearance, including the use of hormones and reconstructive surgery."