Naloxone, the standard treatment for heroin overdose, is a safe and effective prescription drug commonly administered by emergency room physicians or first responders acting under standing orders of physicians. High rates of overdose deaths and widely accepted evidence that witnesses of heroin overdose are often unwilling or unable to call 9-1-1 has led to interventions in several US cities and abroad in which drug users are instructed in overdose rescue techniques and provided a "take-home" dose of naloxone. Under current Food and Drug Administration (FDA) regulations, such interventions require physician involvement. As part of a larger study to evaluate the knowledge and attitudes of doctors towards providing drug treatment and harm reduction services to injection drug users (IDUs), we investigated physician knowledge and willingness to prescribe naloxone. Less than one in four of the respondents in our sample reported having heard of naloxone prescription as an intervention to prevent opiate overdose, and the majority reported that they would never consider prescribing the agent and explaining its application to a patient. Factors predicting a favorable attitude towards prescribing naloxone included fewer negative perceptions of IDUs, assigning less importance to peer and community pressure not to treat IDUs, and increased confidence in ability to provide meaningful treatment to IDUs. Our data suggest that steps to promote naloxone distribution programs should include physician education about evidence-based harm minimization schemes, broader support for such initiatives by professional organizations, and policy reform to alleviate medicolegal concerns associated with naloxone prescription. FDA re-classification of naloxone for over-the-counter sales and promotion of nasal-delivery mechanism for this agent should be explored.