OBJECTIVES:   Substance abuse (SA) represents a significant public health problem that impacts tens of millions of persons in the US and imposes over $400 billion in annual economic costs on a national basis in the form of lost productivity, premature death, criminal activity and use of medical care.  The objective of this study was to estimate the economic costs associated with drug and alcohol abuse for Washington State in 2005. METHODS: We used standard cost of illness (COI) methods, relying on the prevalence approach,  to estimate the costs of SA in six areas, including mortality, morbidity, treatment costs, crime, and health care.  We obtained data for the analysis from various sources, including the Washington State Health Department, the National Survey on Drug Use and Health, the State Department of Corrections, and the Washington Association of County Sheriffs, and the Washington State Department of Transportation. RESULTS: We estimated costs of SA for 2005 for Washington State at $5.21 billion, $832 per non-institutionalized person in the state.  Alcohol abuse accounted for 56% of total costs.  The per-capita, inflation-adjusted costs increased by 47% from 1996.  Categories accounting for the greatest costs were mortality ($2.03 billion), crime ($1.09 billion), morbidity ($1.03 billion) and health care ($791 million).  There were 3,224 deaths (7% of all deaths), 89,000 years of productive life lost, and 29,000 hospital discharges in 2005 in Washington associated with SA.  CONCLUSIONS:   SA imposes significant costs on society.  Its economic costs far outweigh the resources expanded to treat persons with SA.  For every $1 dollar the state collected in tax revenue for treatment from alcohol sales in 2005, $20 in economic loss was incurred from alcohol abuse.  Renewed attention needs to be directed at finding more effective ways to reduce the economic and human loss arising from SA.