Abstract: This report focuses on individual, situational and organisational risk factors for overdoses and how they can be modified to reduce fatal outcomes. Key risk and protective factors were categorised and their efficacy and the factors that facilitate or impede prevention were critically discussed by an expert panel. The review evidenced that many interventions may reduce overdose, particularly in settings where the drug user is in contact with treatment or emergency services. Specific interventions are proved to be effective (e.g. pharmacological treatment). At the population level, where many drug users are not in contact with services, overdose reduction depends on behavioural change (e.g. avoiding the mixture of opiates and depressant drugs). Overdose prevention involves personal and societal issues calling for multifaceted intervention.