Drawing on an analysis of data from over 30 cohort studies, it can be estimated that between 10.000 and 20.000 opioid users die each year in Europe. Typically, annual mortality rates are between 10-20/1000, representing an excess mortality 10 to 20 times greater than expected. Most deaths occur among males in their mid-thirties. Four broad categories of cause of death can be identified: overdoses, diseases, suicide and trauma. While the long term trend in HIV related mortality among drug users is downwards, other causes of mortality have shown little sign of decreasing in recent years. Of particular concern are overdoses which account for 6300 to 8400 deaths reported annually. The fact that deaths have not decreased is surprising given the scaling up of treatment and other services. Opioid substitution treatment in particular is known to be protective and the numbers of those in substitution treatment in Europe has increased dramatically. A number of interrelated factors may help explain this intractable problem. These include: the possibility of an aging cohort becoming more vulnerable; the use of alcohol and other drugs; high levels of ill-health, risk behaviour, and co-morbidity; and social exclusion and marginalisation. Reducing overall morbidity among heroin users remains a key issue for Europe's public health services. More efforts are required to better understand and target both the direct and indirect factors associated with mortality among problem drugs users, if this major health cost associated with drug consumption is to be reduced.