Rett syndrome is a devastating disorder that affects numerous physiological functions. This Review by Dr. Ana Paula Abdala of Bristol University (UK), Prof. John Bissonnette of Oregon Health and Science University (USA) and Dr. Adrian Newman-Tancredi, Chief Scientific Officer of Neurolixis, examines the therapeutic potential of drugs that activate serotonin 5-HT1A receptors (read Abstract). Such drugs, including NLX-101, could potentially ameliorate symptoms including autonomic dysfunction (e.g. breathing difficulties), mood deficits (e.g. anxiety) and motor dysfunction (e.g. dystonia).