Inherited disorders of haemostasis predisposing to bleeding (platelet defects; deficiencies in von Willebrand and clotting factors) do not fully protect against the occurrence of thrombotic events. For patients affected with such disorders, antithrombotic treatments, which carry an additional haemorrhagic risk, are very challenging. There are no evidence-based recommendations, but only expert consensus at best. In this narrative review, we describe the epidemiology of the thrombotic risk in such a setting, and propose some basic rules for a structured reasoning and examples of the guidance on the utilization of antithrombotic drugs. Antithrombotic therapy for such patients, who are managed by specialized teams on a life-long basis, is performed case-by-case, and should involve all caregivers including GPs in a concerted manner.