Many states and local areas are affected by the national epidemic of drug-related mortality, which recently has shown signs of a rising "licit-to-illicit drug" death ratio. Appropriate local public health surveillance can help monitor and control this epidemic. Using our state as an example, we sought to illustrate how to describe the changes in drug death rates, causes, and circumstances. In contrast to most other surveillance reports, our approach includes both drug-induced and drug-related deaths as well as both demographic and socioeconomic characteristics of decedents. Cross-sectional study. All residents of the state of Wisconsin. Decedents from 1999 to 2008. Annual numbers and population-based rates of deaths due to drugs, including both identified and unidentified drugs. Information was obtained from death certificates with any of approximately 270 underlying, immediate, or contributing cause-of-death codes from the International Classification of Diseases, 10th Revision. Drug-related death rates increased during much of the 10-year study period, and the male-to-female death ratio rose. The median age at death from drug-related causes was 43 years. Opioid analgesic poisoning surpassed cocaine and heroin poisoning as the most frequent type of fatal drug poisoning. Of all 4828 deaths from drug-related causes--virtually all of which were certified by a county medical examiner or coroner--3410 (71%) were unintentional and 1053 (22%) were suicides. The unintentional-to-suicide death rate ratio grew from 1.6 to 3.5 during the study period. Methadone-related deaths increased from 10 in 1999 to 118 in 2008 (1080%), while benzodiazepine-related deaths rose from 23 to 106 (361%). Although premature deaths from drug use and abuse continue to rise, even surpassing deaths due to motor vehicle crash in some states, "multiple causes of death" information from death certificates is available to monitor their occurrence and nature and to inform selection of prevention strategies.