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This article explores trends and correlates of Chicago’s opiate-related overdose (OD) deaths. We manually examined data from every death certificate filed between 1999 and 2003 to identify all Chicago residents’ accidental deaths involving acute intoxication with illicit opiates, OD, or opiate poisoning. The analysis includes an examination of contextual characteristics in 77 Chicago neighborhoods. Negative binomial regression analysis permits the calculation of incidence rate ratios (IRR) associated with time trends. OD incidence peaked in 2000 and then declined markedly by 2003 [year 2000–2003 IRR = 0.65, 95% confidence interval (CI) (0.54, 0.78)]. Over the 2000–2003 period, overall incidence of fatal OD declined by 34%. Over this period, the sharpest observed declines occurred among African-Americans [IRR = 0.64, 95% CI (0.51, 0.81)] and Hispanics/Latinos [IRR = 0.53, 95% CI (0.32, 0.88 …