Flaviviruses are a group of positive-stranded RNA viruses that cause a spectrumof severe illnesses globally in more than 50 million individuals each year.While effective vaccines exist for three members of this group (yellow fever,Japanese encephalitis, and tick-borne encephalitis viruses), safe and effectivevaccines for several other flaviviruses of clinical importance, including WestNile and dengue viruses, remain in development. An effective humoral immuneresponse is critical for protection against flaviviruses and an essential goalof vaccine development. The effectiveness of virus-specific antibodies in vivoreflects their capacity to inhibit virus entry and spread through severalmechanisms, including the direct neutralisation of virus infection. Recentadvances in our understanding of the structural biology of flaviviruses, coupledwith the use of small-animal models of flavivirus infection, have promotedsignificant advances in our appreciation of the factors that govern antibodyrecognition and inhibition of flaviviruses in vitro and in vivo. In this review,we discuss the properties that define the potency of neutralising antibodies andthe molecular mechanisms by which they inhibit virus infection. How recentadvances in this area have the potential to improve the development of safe andeffective vaccines and immunotherapeutics is also addressed.