CDKL5 deficiency disorder (CDD), also known as developmental epileptic encephalopathy, is a rare X-linked dominant disease of the nervous system. Its main clinical manifestations include: uncontrollable seizures, cognitive impairment, motor retardation, visual impairment, sleep disorders, gastrointestinal impairment, autonomic nervous dysfunction, and autistic like manifestations. Its high disability rate and heavy disease burden bring heavy burden to society and family. However, the current domestic and foreign studies on this disease mainly focus on the clinical phenotype and pathogenesis, and there are few studies involving the standard clinical management of various systems. Therefore, a core committee composed of CDD experts from the United States, Europe, and the United Kingdom conducted a six-month investigation (August 2020—January 2021) and developed the international consensus: recommendations for the assessment and management of CDKL5 deficiency patients (hereafter referred to as the Consensus) based on the Durfel research methodology. This consensus invites multidisciplinary experts to put forward diagnosis and treatment suggestions for the diagnosis and treatment of CDD as well as the clinical management of various systemic systems, which will provide evidence-based basis for regulating the diagnosis and treatment behaviors of clinicians for CDD. In this paper, the consensus was interpreted to facilitate the long-term management of the disease.