People with mental retardation (MR) and addiction are an especially vulnerable population, yet evidence-based approaches to substance abuse (SA) treatment for this group are limited. Research suggests that SA-related services for this population are most likely received in nonaddiction settings that are generally focused on provision of mental health services to populations with MR and that might be unequipped for this work. This fact, combined with documented challenges to cross-system collaboration, suggests the potential for discontinuities in care for people with MR and SA. Recommendations for SA screening and a framework for cross-system collaboration are presented with specific recommendations for the ways in which social workers in both MR and SA service settings can promote positive client outcomes.