The burden of mental illness is profound and growing. Coupled with large gaps in extant psychiatric services, this mental health burden has often forced emergency departments (EDs) to become the de facto primary and acute care provider of mental health care in the United States. An expanded emergency medical and mental health research agenda is required to meet the need for improved education, screening, surveillance, and ED-initiated interventions for mental health problems. As an increasing fraction of undiagnosed and untreated psychiatric patients passes through the revolving doors of U.S. EDs, the opportunities for improving the art and science of acute mental health care have never been greater. These opportunities span macroepidemiologic surveillance research to intervention studies with individual patients. Feasible screening, intervention, and referral programs for mental health patients presenting to general EDs are needed. Additional research is needed to improve the quality of care, including the attitudes, abilities, interests, and virtues of ED providers. Research that optimizes provider education and training can help academic settings validate psychosocial issues as core components and responsibilities of emergency medicine. Transdisciplinary research with federal partners and investigators in neuropsychiatry and related fields can improve the mechanistic understanding of acute mental health problems. To have lasting impact, however, advances in ED mental health care must be translated into real-world policies and sustainable program enhancements to assure the uptake of best practices for ED screening, treatment, and management of mental disorders and psychosocial problems.