To quantify the public health and economic burden of endemic canine rabies in Africa and Asia. Data from these regions were applied to a set of linked epidemiological and economic models. The human population at risk from endemic canine rabies was predicted using data on dog density, and human rabies deaths were estimated using a series of probability steps to determine the likelihood of clinical rabies developing in a person after being bitten by a dog suspected of having rabies. Model outputs on mortality and morbidity associated with rabies were used to calculate an improved disability-adjusted life year (DALY) score for the disease. The total societal cost incurred by the disease is presented. Human mortality from endemic canine rabies was estimated to be 55 000 deaths per year (90% confidence interval (CI) = 24 000-93 000). Deaths due to rabies are responsible for 1.74 million DALYs lost each year (90% CI = 0.75-2.93). An additional 0.04 million DALYs are lost through morbidity and mortality following side-effects of nerve-tissue vaccines. The estimated annual cost of rabies is USD 583.5 million (90% CI = USD 540.1-626.3 million). Patient-borne costs for post-exposure treatment form the bulk of expenditure, accounting for nearly half the total costs of rabies. Rabies remains an important yet neglected disease in Africa and Asia. Disparities in the affordability and accessibility of post-exposure treatment and risks of exposure to rabid dogs result in a skewed distribution of the disease burden across society, with the major impact falling on those living in poor rural communities, in particular children.