Issues: Despite the serious implications of loneliness on health and wellbeing, little is understood about this experience across people with substance use problems. This systematic review aimed to examine: (i) correlates and predictors of loneliness; (ii) theories underpinning loneliness; (iii) methods employed to measure loneliness; and (iv) loneliness interventions for people with substance use problems. Approach: Empirical sources were identified from key databases for all publications preceding February 2019. Overall, 41 studies met the eligibility criteria and were included in the review. Key Findings: Findings from this review suggest that loneliness is related to poor physical and mental health, substance use, the quality of relationships, stigma and perception of ill treatment by others. Although cognitive theories have proposed cognitive patterns underlying the onset and maintenance of loneliness, they had not been investigated in relation to measurement or intervention efforts. Just one loneliness measure (UCLA Loneliness Scale) is valid for use with this population. Finally, only a single loneliness intervention had been trialled and was not found to be efficacious in reducing loneliness for people with substance use problems. Implications: Understanding possible links between loneliness and substance use and how to alleviate loneliness is important for this population in terms of their wellbeing and recovery. Conclusion: Loneliness is prevalent and experienced as problematic among people with substance use problems. Future research should focus on employing longitudinal designs, using validated, multidimensional measures of loneliness and on developing and trialling loneliness interventions that meet the specific needs of people with substance use problems.