[1] He previously was the director of the Center for Genetic Medicine Research at Children's National Medical Center and the chair of the Department of Genomics and Precision Medicine at the George Washington University School of Medicine & Health Sciences in Washington, D.C.[2][3][4] Vilain is a fellow of the American College of Medical Genetics, serves on the International Olympic Committee's Medical Commission, and sits on the Board of Scientific Counselors for the National Institute of Child Health and Human Development (NICHD).

Vilain is known for his research on the molecular mechanisms of DSDs, using DNA sequencing and animal models to discover the biological bases of sex differentiation.

In addition to DSDs, Vilain has also published a large body of research on sex differences in the brain, the biology of sexual orientation, and gender identity.

[7] His early research focused on the gene SRY and its role in the formation of the testes, as well as how certain mutations could explain diseases such as gonadal dysgenesis.

[13] In 2011, Vilain was one of the members of the International Olympic Committee Medical Commission and helped revise the policies on female athletes with DSDs such as androgen insensitivity syndrome (AIS), spurred by the case of South African runner Caster Semenya in 2009.

[17] In 2006, his team, along with geneticist Dean Hamer, published research studying the linkage of gay males and markers on their mothers' X chromosome.

[18] During the 2015 conference of the American Society of Human Genetics, his team presented findings on potential epigenetic differences in identical male twins discordant in sexual orientation.