Harm reduction (HR) interventions began in Central-Eastern Europe and Central Asia in the mid-1980s with the establishment of substitution treatment (ST) in Yugoslavia. In the mid-1990s, the first needle and syringe programmes (NSPs) opened in selected countries following the outbreaks of HIV among injecting drug users (IDUs). The number of NSPs continues to increase via a combination of international and state funding with large expansions made possible via the Global Fund to Fight AIDS, Tuberculosis and Malaria. While ST is still unaccepted in several countries, others have made some progress which is especially visible in South Eastern and Central Europe and the Baltic States. Development of regional networking including Central and Eastern European HR Network and a number of national networks helped to coordinate joint advocacy effort and in some cases sustain HR services. Activism of drug users and people living with HIV (PLWH) increased in the region in the last several years and helped to better link HR with the affected communities. Still a number of challenges remain important for the movement today such as repressive drug policies; stigma and discrimination of IDUs, PLWH, sex workers and inmates, including poor access to prevention and treatment; lack of important components of HR work such as naloxone distribution and hepatitis B vaccination, prevention in prisons; issues of quality control; sustaining services after finishing of major international projects; reaching of adequate coverage and others.