International studies have explored the use of community-based nurses for harm reduction programs and HIV prevention. However, none have explored this role within the countries of Nepal, Myanmar, and China where the legal and political environment may adversely affect uptake of services by people who use injection drugs. Based on experiences as a nurse and harm reduction technical adviser for the development of community-based nursing initiatives in Nepal, Myanmar and China, I review some of the strengths and challenges associated with harm reduction programs in these countries. Community-based nurses play an important role in increasing the access and uptake of public health services by people who inject drugs. Within the context of harm reduction programs, community-based nurses develop a unique trust with people who inject drugs by providing non-discriminatory health care. Nurses act as information bridges between communities of people who use injection drugs, law enforcement, political and health care stakeholders. In doing so, they facilitate timely policy and programmatic responses. However, community-based nurses are prone to burnout due to long working hours and a limited pool of human resources. Community-based nurses have proven essential to the effective implementation of harm reduction program for HIV prevention in Nepal, Myanmar and China. Increased attention and support to these health care professionals have the potential to strengthen existing programs targeting people who inject drugs.