Rett syndrome, a rare genetic disease caused by mutations of the MECP2 gene, includes severe to profound developmental impairments. Communicative, intellectual, and motor disabilities are usually embedded. Children with Rett syndrome are individuals with multiple difficulties. Caregivers, families and professionals face to serious daily challenges due to clinical conditions determined by Rett syndrome. Accordingly, traditional interventions may not be adequate. Customized programs based on cognitive-behavioral approaches and assistive technology setups are highly warranted. The current book includes the newest empirical contributions to tackle functional consequences of Rett syndrome. Sleep and pain disorders were targeted in Chapter One. A cross-disciplinary investigation to enhance active participation and constructive engagement of children with Rett syndrome was detailed in Chapter Two. The importance of functional activities was emphasized in Chapter Three. Communication guidelines to support communication skills of individuals with Rett syndrome were critically discussed in Chapter Four. The relevance of music and music therapy to promote positive participation was argued in Chapter Five. A selective review on the use of assistive technology-based programs in individuals with Rett syndrome was provided in Chapter Six. A case report to help locomotion fluency of an adolescent with Rett syndrome through the use of microswitches and contingent positive stimulation was presented in Chapter Seven. The book was supported by illustrative examples described by the chapters' contributors and their professional experience. Readers may find helpful insights within each edited chapter. Caregivers, families, and professionals may have a practical guide to everyday settings and environments or contexts. Clarity and readability for a large audience are undoubtedly strengths and advantages of the current volume. Although technical terminology was used throughout, both future research and practice can widely find meaningful tips and tangible suggestions to tackle daily barriers and/or obstacles in individuals with Rett syndrome and severe to profound developmental delays.