Severe drug-induced liver injury is a relatively rare but important public health problem. Extrapolating the incidence of this problem from clinical treatment trials is confounded by a number of issues, including the relatively small size of clinical trials, exclusion criteria for study participation, and active surveillance for liver injury. Advances in understanding the pathogenesis of drug-induced liver injury, as well as its prevention and treatment, will likely require the identification and careful characterization of severe cases in the post-marketing, "real-world" setting as part of a concerted, multi-center, well-orchestrated effort. The Drug-Induced Liver Injury Network (DILIN) represents one example of such an effort.