Afghanistan leads global opium and cannabis production, amidst concerted efforts to improve the country’s infrastructure. In this commentary, the evidence base for drivers of increased drug use in the context of deteriorating security is presented, government, donor, and civil society responses to date are described, and key areas for health policy response are summarized. Opiate use in Afghanistan shows disturbing trends: multiple substances are accessible at low cost and frequently used in combination, and injecting use has become more common. Pressures from both donor and governmental sectors have compromised innovations in programming. Further, civil unrest and resultant displacement have created challenges for programme implementation. Afghanistan urgently needs a well-funded, sustainable, comprehensive, and inclusive programme of drug dependency treatment, aftercare, and harm reduction services, as well as realistic, effective, and culturally salient primary prevention programmes. To date, drug dependence is not a prioritised issue, current programmes are under-resourced, and the continuum of care has a narrow scope generally limited to treatment. Unless this issue is addressed, the next generation of Afghans is poised to become a casualty of the opiate industry.