This systematic review evaluated the evidence for use of computer technologies to assess and reduce high-risk health behaviors in emergency department (ED) patients. A systematic search was conducted of electronic databases, references, key journals, and conference proceedings. Studies were included if they evaluated the use of computer-based technologies for ED-based screening, interventions, or referrals for high-risk health behaviors (e.g., unsafe sex, partner violence, substance abuse, depression); were published since 1990; and were in English, French, or Spanish. Study selection and assessment of methodologic quality were performed by two independent reviewers. Data extraction was performed by one reviewer and then independently checked for completeness and accuracy by a second reviewer. Of 17,744 unique articles identified by database search, 66 underwent full-text review, and 20 met inclusion criteria. The greatest number of studies targeted alcohol/substance use (n = 8, 40%), followed by intentional or unintentional injury (n = 7, 35%) and then mental health (n = 4, 20%). Ten of the studies (50%) were randomized controlled trials; the remainder were observational or feasibility studies. Overall, studies showed high acceptability and feasibility of individual computer innovations, although study quality varied greatly. Evidence for clinical efficacy across health behaviors was modest, with few studies addressing meaningful clinical outcomes. Future research should aim to establish the efficacy of computer-based technology for meaningful health outcomes and to ensure that effective interventions are both disseminable and sustainable. The number of studies identified in this review reflects recent enthusiasm about the potential of computers to overcome barriers to behavioral health screening, interventions, and referrals to treatment in the ED. The available literature suggests that these types of tools will be feasible and acceptable to patients and staff.