Some research questions can only be answered by members of a vulnerable group. Frequently members of these groups are doubly vulnerable as they experience more than one factor that diminishes their autonomy. Initiating research with doubly vulnerable persons presents unique and often difficult challenges. Because of these challenges, many researchers purposefully exclude doubly vulnerable groups from research endeavours. Thus, the health care needs and concerns of individuals considered doubly vulnerable are often not addressed in the scientific literature. This article presents two challenges frequently encountered when initiating research with doubly vulnerable populations: resolving pre-investigation issues and gaining access to vulnerable populations. Ethically sound strategies for confronting these challenges are discussed. Researchers' experiences with doubly vulnerable populations are also incorporated. Only when doubly vulnerable groups receive the appropriate research attention are the standards of their care and their quality of life enhanced.