Maternal separation (MS) is defined as the termination of the continuity of mother-child relationship after the relationship is established. Although MS and maternal deprivation are different in terms of their definitions, these two terms are usually used interchangeably. This review aims to investigate the effect of MS on drug intake in adulthood. It has been proved that animal models are helpful in evaluating the effects of MS on drug intake risk in adulthood. There are relatively acceptable studies in this field on some drugs such as morphine, ethanol, and cocaine. However, very few animal studies, or even no animal study, have been conducted on some other drugs. The majority of these studies have considered MS as a risk factor for drug intake in adulthood. Different mechanisms are proposed for this phenomenon. Brain reward pathways are one of the main exploratory pathways of this process. Despite the importance of the issue, no human study with a specific concentration on investigating the relationship between MS and drug abuse in later life was found. Causal studies are warranted on humans to investigate the effect of MS on drug intake in later life.