This article reviews the current body of knowledge on the adverse effects of smoking on soft-tissue and bone healing, with emphasis on tibial fractures in combination with severe soft-tissue injury. The pathophysiological effects are multidimensional, including arteriolar vasoconstriction, cellular hypoxia, demineralisation of bone, and delayed revascularisation. Several animal and clinical studies have been published about the negative effects of smoking on bone metabolism and fracture healing. These studies show that smokers have a significantly longer time to clinical union than non-smokers and a higher incidence of non-union. The negative effects of smoking gained increased interest among plastic and microvascular surgeons, because smokers have been shown to suffer higher rates of flap failure, tissue necrosis, and haematoma formation. Especially smokers presenting with an open tibial fracture will suffer the negative effects of their smoking behaviour, because these fractures are inextricably bound up with soft-tissue injury. Their fractures will need a significantly longer time to heal than in non-smokers, and will have a higher incidence of non-union. If microvascular surgery is to be performed, persistent smoking significantly increases the rate of postoperative complications, with wound infection, partial flap necrosis, and skin graft loss being more common. Cessation of smoking has both short- and long-term beneficial effects. Nowadays, there is strong evidence to be very insistent that patients presenting with a (open) tibial fracture should refrain from smoking immediately to promote bone healing and to lower the complication rate. In case of elective reconstructive procedures, patients should refrain from smoking at least 4 weeks before surgery. In both situations, cessation should continue during the full rehabilitation period.