PURPOSE OF REVIEW: HIV infection rates continue to rise among people who inject drugs (PWID) in many lower- and middle-income countries (LMICs). Although progress is being made in prevention and care for PWID in some settings, coverage of essential services remains low. This article reviews the evidence for the benefits of scaling up key interventions as a combination prevention and treatment package for PWID. RECENT FINDINGS: WHO defined a comprehensive package of nine interventions for PWID, of which the following four have evidence for effectiveness in reducing HIV incidence: needle and syringe programs (NSP), medication-assisted therapy (MAT), antiretroviral therapy (ART), and HIV counseling and testing (HCT). Coverage of these interventions among PWID in LMICs varies from low (≤20%) to medium (>20-60%). At least a 60% coverage is likely to be required to reduce HIV incidence. Evidence from LMIC contexts suggests that NSP and MAT can reduce high-risk injecting behavior, HCT can reduce risky sexual behavior and ART can plausibly have preventive benefit among PWID for onward parenteral transmission with clearer evidence that antiretroviral therapy (ARV) can prevent onward sexual transmission. Modeling analysis suggests that compared with current low coverage, a scale-up of these four interventions in combination would be a beneficial and cost-effective approach. SUMMARY: The continuation of significant HIV incidence among PWID in LMIC settings is avoidable with the implementation of immediate scale-up of key harm reduction and ARV treatment interventions. Policymakers should address the structural and resource allocation barriers to allow this scale-up to occur.