Background: Utero-vaginal agenesis, also called the Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH), is a congenital abnormality of the female genital tract, characterized by the non-formation of the vagina and the uterus. It is a common cause of primary amenorrhoea. Little is known about the psychological impact and management of this condition. Method: We describe a specific model of the core negative psychological impact of diagnosis and medical treatment of MRKH and a cognitive-behavioural therapy of MRKH based on the model (CBT-MRKH). The Medical Research Council's (2002) framework for the development and evaluation of complex health interventions was used for intervention development and evaluation. Results: Evidence from a recent cross-sectional study and a small randomized controlled trial (RCT) provides preliminary support for the model and treatment (Heller-Boersma, Schmidt and Edmonds, in press; Heller-Boersma, Schmidt and Edmonds, 2007), and this is further validated by extensive qualitative material gathered over the course of the RCT from participants. Conclusions: The model and treatment described may also be applicable to a number of other congenital or acquired gynaecological conditions such as premature ovarian failure, breast cancer, early onset endometrial cancer, female genital mutilation, Turner's Syndrome, ovarian dys/agenesis or, Complete Androgen Insensitivity Syndrome, all of which have a psychological impact not dissimilar to MRKH in terms of these women's sense of self and femininity.