Drug-induced liver injury(DILI) and herb-induced liver injury is a hot topic for clinicians,academia,drug companies and regulators,as shown by the steadily increasing number of publications in the past 15 years.This review will first provide clues for clinicians to suspect idiosyncratic(unpredictable) DILI and succeed in diagnosis.Causality assessment remains challenging and requires careful medical history as well as awareness of multifaceted aspects,especially for herbs.Drug discontinuation and therapy reconciliation remain the mainstay in patent’s management to minimize occurrence of acute liver failure.The second section will address novel agents associated with liver injury in 2014(referred to as “signals”),especially in terms of clinical,research and drug development implications.Insights will be provided into recent trends by highlighting the contribution of different post-marketing data,especially registries and spontaneous reporting systems.This literature scrutiny suggests:(1) the importance of postmarketing databases as tools of clinical evidence to detect signals of DILI risk;and(2) the need for joining efforts in improving predictivity of pre-clinical assays,continuing post-marketing surveillance and design ad hoc post-authorization safety studies.In this context,ongoing European/United States research consortia and novel pharmaco-epidemiological tools(e.g.,specialist prescription event monitoring) will support innovation in this field.Direct oral anticoagulants and herbal/dietary supplements appear as key research priorities. Drug-induced liver injury (DILI) and herb-induced liver injury is a hot topic for clinicians, academia, drug companies and regulators, as shown by the steadily increasing number of publications in the past 15 years. This review will first provide clues for clinicians to suspect idiosyncratic (unpredictable) DILI and succeed in diagnosis. Causality assessment yet challenging and not careful medical history as well as awareness of multifaceted aspects, especially for herbs. Drug discontinuation and therapy reconciliation remain the mainstay in patent’s management to minimize occurrence of acute liver failure. The second section will address novel agents associated with liver injury in 2014 (referred to as “signals ”), especially in terms of clinical, research and drug development implications. Insights will be provided into recent trends by highlighting the contribution of different post-marketing data, especially registries and spontaneous reporting systems. This literature scrutiny suggests: (1) the importance of postmarketing databases as tools of clinical evidence to detect signals of DILI risk; and (2) the need for joining efforts in improving predictivity of pre-clinical assays, continuing post-marketing surveillance and design ad hoc post-authorization safety studies.In this context, ongoing European / United States research consortia and novel pharmaco-epidemiological tools (eg, specialist prescription event monitoring) will support innovation in this field. Direct oral anticoagulants and herbal / dietary supplements appear as key research priorities.