Edinburgh and Glasgow are only 50 miles apart but their contrasting geography, history and economy have made them vastly different places in which to live. The average life expectancy of people in Edinburgh is about 4 years longer than in Glasgow. This reflects the much greater levels of socio-economic deprivation in Glasgow where 30% of the population live in areas categorised as the most deprived, compared with only 3% in Edinburgh. Across Scotland, harmful drug and alcohol misuse is more strongly related to socio-economic deprivation than any other variable. This largely explains the much greater levels of drug misuse and alcohol related harm in Glasgow than in Edinburgh. In the early 1980s, both cities experienced an epidemic of drug injecting. HIV arrived earlier and spread more quickly in Edinburgh than in Glasgow, possibly due to more intensive needle sharing. Edinburgh quickly responded with a successful methadone programme cutting both injecting and HIV rates. Glasgow went for needle exchange which was sufficient to prevent significant spread of HIV but not hepatitis C. Glasgow only developed a methadone programme from 1994 onwards, introducing pharmacy supervised consumption on a large scale. Edinburgh’s provision of unsupervised methadone has led to far more methadone related deaths and non-prescribed methadone dependence than in Glasgow. Death from heroin overdose is common in Glasgow, rare in Edinburgh. In responding to drug related harm, both cities have had conspicuous success but the fatal lure of drugs, particularly to their disenfranchised youth, seems greater than ever in both cities today.