 Hand foot and mouth disease HFMD is a common infectious disease caused by a variety of enteroviruses. A small proportion of those infected with enterovirus 71 EV71 develop neurological and systemic complications that may prove fatal. Over the past 15 years EV71 related HFMD has caused increasing epidemics of HFMD across Asia; in 2011, in excess of 100,000 Vietnamese children were diagnosed clinically with HFMD and 164 died. The neurological problem of most concern is brainstem encephalitis, causing autonomic nervous system ANS dysregulation that may progress rapidly to cardiopulmonary failure. Management of ANS dysregulation is difficult even in sophisticated western intensive care units. The phosphodiesterase-3 inhibitor, Milrinone, was reported to control hypertension and support myocardial function in a small informal study of severe HFMD compared to historical controls, but in practice treatment remains largely empirical. ANS dysregulation also occurs in severe tetanus and there is a body of evidence indicating that intravenous magnesium sulphate Mg is effective in controlling tetanus-associated cardiovascular instability. Mg is also used widely for eclampsia, severe asthma and pulmonary hypertension, and there are reports of rapid control of life-threatening autonomic hyperreflexia in patients with spinal lesions. Formal safety data in children are limited, but adverse effects appear to be infrequent. In a series of 24 severe EV71 confirmed HFMD cases managed recently at the Hospital for Tropical Diseases, Ho Chi Minh City, Mg was added when hypertension remained poorly controlled despite high-dose Milrinone. In all cases the blood pressure BP reduced within 30-60 minutes and remained stable subsequently on a continuous Mg infusion for 48-72 hours. 