This chapter describes the acculturative stress related to migration. The stress occurs as a result of cultural and psychological changes and can lead to mental health problems. Human migration has existed for centuries. The process of globalisation, which has recently affected all regions of the world, has also greatly impacted upon the mental health status of many of the migrants. There are a series of variables that play a major or minor role in the process of acculturation and in the level of acculturative stress. The behavioural variables are the ones that more traumatically and negatively impact on the migrant groups. Substance use/abuse is another behavioural variable related to the process of acculturation and to the negative impact of acculturative stress on migrant/minority populations as they interact and have contact with the majority/host society. Stress has certainly existed since humans became a part of the universe.