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Designing education for learners with profound intellectual and multiple disabilities (PIMD) is a special challenge for both professionals and researchers. Learners with PIMD experience a combination of significant intellectual and other disabilities, such as motor and sensory impairments. Heterogeneity in terms of combination and severity of disabilities is a common characteristic of this group. In the past, learners in this target group were described as not being able to learn due to the complexity of their disabilities. Recent studies do provide evidence that learners with PIMD are in fact able to learn, however, evidence-based practice for designing education for this group of learners is still scarce. One reason could be the difficulties associated with conducting intervention studies such as randomized controlled trials or controlled clinical trials with this target group. Most studies are designed as single-case studies. Hence, only a small number of studies have investigated topics such as communication, assessment, and teaching curricula to generate knowledge about the education of these learners. The most important conclusion of these studies is that all teaching activities need to be designed according to the strengths and needs of each individual learner with PIMD.