There is an increasing national and world-wide recognition of the pressing need for improved health and welfare of transgender individuals, who usually feel isolated and marginalised from health systems and wider society. Emerging evidence supports a biological basis for gender dysphoria. Although accurate prevalence and incidence figures remain difficult to ascertain, the presentation of transgender people seeking health professional advice and care has risen strikingly in recent years. The successful management of gender dysphoria requires careful attention to the timing and sequence of medical interventions during transition as well as ongoing, long-term empathetic and skilled medical care. The persistent and intolerable mismatch between their gender identity and assigned natal sex can usually be reconciled through a combination of psychological, medical and surgical interventions; however, the sequence and timing of interventions depends on careful balance of their life circumstances including barriers to successful management. Cross sex hormone therapy with its monitoring and adverse effects will be outlined. Transgender individuals frequently have co-morbidities, notably mental health problems and substance abuse, which complicate smooth and successful gender transition as well as long-term care. Major needs for further research are the long term cardiovascular and bone health outcomes as well as quality of life and potential regret, all of which will be reviewed based on current evidence.