This chapter provides a theoretical understanding of the nature and extent of substance use among refugees. A theoretical model of self-medication is constructed and illustrated by means of data obtained from empirical research among refugees. The chapter presents a review of existing empirical studies of asylum seekers and refugees in Europe, North America and Australia. It argues that because refugees have few resources in their host country, little control over their new situation and/or few personal resources, they are vulnerable to the problematic use of alcohol, prescription medication and illegal drugs. Conservation of resources theory is based on the premise that individuals strive to obtain, retain and protect that which they value - their ‘resources.’ The self-medication hypothesis postulates that substances are used as a means of achieving relief from symptoms of pre-existing stress and stress-related psychiatric disorders. Despite the vulnerability of many refugees to substance use, several protective factors need to be taken into account.