In this article we report trends in deaths related to drug misuse in England and Wales from 1993 to 2004, looking particularly at the period between 1999 and 2004, for which there was a Government target to reduce these deaths by 20 per cent. Although there was an overall decline in deaths related to drug misuse between 1999 and 2004, the percentage reduction, at 9 per cent, was less than the Government target. There was an increase in deaths between 2003 and 2004, largely accounted for by deaths involving heroin/methadone and morphine. Mortality rates were highest in young adults and an increase in mortality rates within this group appears to have been the driver behind rising mortality trends during the 1990s.