Launched in 1993 and partially based on the results of an international consensus meeting organized under the auspices of the Council of International Organizations of Medical Sciences (CIOMS), the Roussel Uclaf Causality Assessment Method (RUCAM) is the most used causality assessment tool worldwide for the diagnosis of drug-induced liver injury (DILI) and herb-induced liver injury (HILI) in a large number of epidemiological studies, case reports, and case series. The 25-year experience of RUCAM use confirmed that the success was due to its objective, standardized, and liver-injury-specific approach structured with defined key elements derived from a series of DILI cases with positive rechallenge. Using this series, the validation procedure avoided arbitrary definitions and confirmed scores to key items. The algorithm provides a quantitative causality grading of highly probable, probable, possible, unlikely, or excluded relationship between the liver injury and the suspected product(s). Despite challenges, prospective use of RUCAM fosters case data completeness and transparent causality adjudication in real time, as opposed to subjective opinion resulting from several rounds by experts lacking defined key elements and scores. In 2016, RUCAM was updated with specification of alcohol use and Hepatitis E Virus (HEV) biomarkers and simplified item handling to further reduce inter-observer variability. RUCAM-based probable and highly probable DILI and HILI cases are essential for the detection of new hepatotoxins, confirmation of new biomarkers, description of clinical features and risk factors, and determination of incidence in pharmacoepidemiological studies. This article is intended to encourage systematic use of sophisticated causality assessment methods such as RUCAM to improve DILI and HILI case evaluation and to increase confidence in published cases.