Craniosynostosis describes the premature fusion of one or more cranial sutures 
and can lead to dramatic manifestations in terms of appearance and functional 
impairment. Contemporary approaches for this condition are primarily surgical 
and are associated with considerable morbidity and mortality. The additional 
post-operative problems of suture refusion and bony relapse may also necessitate 
repeated surgeries with their own attendant risks. Therefore, a need exists to 
not only optimize current strategies but also to develop novel biological 
therapies which could obviate the need for surgery and potentially treat or even 
prevent premature suture fusion. Clinical studies of patients with syndromic 
craniosynostosis have provided some useful insights into the important signaling 
pathways and molecular events guiding suture fate. Furthermore, the highly 
conserved nature of craniofacial development between humans and other species 
have permitted more focused and step-wise elucidation of the molecular 
underpinnings of craniosynostosis. This review will describe the clinical 
manifestations of craniosynostosis, reflect on our understanding of syndromic 
and non-syndromic craniosynostoses and outline the different approaches that 
have been adopted in our laboratory and elsewhere to better understand the 
pathogenesis of premature suture fusion. Finally, we will assess to what extent 
our improved understanding of the pathogenesis of craniosynostosis, achieved 
through laboratory-based and clinical studies, have made the possibility of a 
non-surgical pharmacological approach both realistic and tangible.