Background: Substance use disorders (SUDs) represent a worldwide epidemic with extensive costs to the individual and to society. Occasionally described as an attachment disorder, they have been linked to various impairments in self-regulation and social functioning. However, while there have been significant advances in the development and validation of treatment strategies for SUD in recent years, the components of these treatment approaches have yet to be fully explored. The characteristics of polydrug use disorder (PUD) especially need to be addressed in more detail, as this diagnosis is highly common in individuals seeking treatment, while simultaneously being associated with poor treatment success. Aim and Scope: This review aims at further exploring the relevance of attachment in PUD and its treatment. To this end, this review provides a concise summary of relevant theories on the development and treatment of SUD in general, including related parameters of attachment, emotion regulation, and neuroscience. Furthermore, several studies focused specifically on PUD are described in more detail. These studies explored the connections between attachment, personality structure, primary and higher emotions (including spirituality), as well as structural and functional neural parameters in inpatients with PUD as well as in healthy controls. Most notably, the described studies highlight that insecure attachment and impairments in personality structure are present in inpatients with PUD. In addition, these characteristics are paralleled by extensive impairments in white matter integrity, especially in tracts connected to facets of emotion regulation. Conclusions: Based on our findings, we emphasize conceptualization of PUD as an Attachment Disorder, on a behavioral as well as on a neural level. Furthermore, we point out the importance of an integrated bio-psycho-social approach in this research area. Consequently, future studies might more closely focus on the influence of attachment-based interventions on emotion regulation abilities as well as a potentially related neuroplasticity. Neuroplastic changes, which are still rather unexplored, might represent important parameters for the assessment of treatment outcomes especially in long-term SUD treatment.