Background: Research into Rett syndrome has included various medical interventions. Non-medical interventions are relatively under-researched. Recent technological communication intervention advances have contributed to the evidence base in Rett syndrome. Method: The Embase, PsycINFO and MEDLINE were systematically searched for peer-reviewed papers describing non-medical interventions for Rett syndrome. All identified papers were evaluated for methodological quality. Results: Thirteen studies of adequate methodological quality were reviewed (across N = 60 participants). Interventions were primarily communication interventions including music, assistive technology, augmentative and alternative communication strategies, attentional training and cognitive rehabilitation training. All studies reported positive outcomes across communication, quality of life, brain stem activity, physical fitness and a reduction in stereotyped behaviour. However, methodological challenges to generalizability, standardization, lack of follow-up and/or small-N samples were common. Conclusions: The review highlights the paucity of high-quality research. Future research is needed to build on current research and improve validity and generalizability of interventions.