Overgrowth-intellectual disability (OGID) syndromes encompass a group of rare neurodevelopmental disorders that frequently share common clinical presentations. Although the genetic causes of many OGID syndromes are now known, we lack a clear mechanistic understanding of how such variants disrupt developmental processes and ultimately culminate in overgrowth and neurological symptoms. Patient advocacy groups, such as the Overgrowth Syndromes Alliance (OSA), are mobilising patients, families, clinicians and researchers to work together towards a deeper understanding of the clinical needs of patients with OGID, as well as to understand the fundamental biology of the relevant genes, with the goal of developing treatments. In this Review, we summarise three OGID syndromes encompassed by the OSA, namely Sotos syndrome, Malan syndrome and Tatton-Brown-Rahman syndrome. We discuss similarities and differences in the biology behind each disorder and explore future approaches that could potentially provide a way to ameliorate some of the unmet clinical needs of patients with OGID.