Non-union of bone following fracture is an orthopaedic condition with a high morbidity and clinical burden. Despite its estimated global prevalence of nine million annually, the limit of bone regeneration therapy still results in patients living with pain, a reduced quality of life and associated psychological, social and financial repercussions. This review provides an overview of the current epidemiological and aetiological data, and highlights where the clinical challenges in treating non-union lie. Current treatment strategies are discussed as well as promising future research foci. Development in biotechnologies to treat non-union provides exciting scope for more effective treatment for this debilitating condition.