The strategies overlap to a considerable extent. Supply reduction and supply reduction policies share a commitment to the use reduction paradigm. Harm reduction offers an alternative perspective. It notes that prevalence reduction policies have left the harms resulting from drug use largely intact and that harsh enforcement policies are a source of many drug-related harms. However, the public and policymakers generally ignore or oppose harm reduction and some forms of quantity reduction. The emphasis on use reduction rather than harm reduction results from several historical factors, but a more basic reason for opposition to harm reduction is the concern that it will send the wrong message. Harm reduction advocates must address this argument if they are to overcome opposition. Harm reduction does have potential pitfalls; not every harm reduction intervention will succeed and some might even increase aggregate harm. Nevertheless, the success of needle exchange programs provides encouragement. Successful harm reduction that both reduces aggregate harm and attracts and retains a viable level of political support should rest on six general principles. Figure and 42 references