Rett syndrome is classified within the rare genetic syndromes, characterised by intellectual delays, extensive motor impairments, lack of speech and communication difficulties, sensorial deficits, and problems in adaptive responding. That clinical conditions may be deleterious on their social image, status, and quality of life. A practice for addressing this problem is technology-based interventions. The use of assistive technologies, in particular microswitches, with children with RTT has been shown to effectively change the impact on their quality of life, facilitating access to recreational activities and improving their performance. Through the use of technology-aided programs, a child with RTT and multiple disabilities will be ensured with an independent access to positive stimulation. In this chapter, a selective literature review was carried out considering Rett Syndrome, assistive technologies, quality of life, and rare genetic syndromes. Empirical data demonstrated the effectiveness and suitability of interventions with AT, allowing participants to increase their level of independence.