Acquired hemophilia (AH) is a rare but severe bleeding diathesis characterized by autoantibodies against a clotting factor, in most cases Factor VIII (FVIII). This bleeding disorder occurs more frequently in the elderly and may be associated with several conditions, such as malignancies, autoimmune diseases, postpartum or drugs; however, about half of cases remain idiopathic. At variance with congenital hemophilia, in which hemarthroses are the most common bleeding manifestations, in patients with AH hemorrhages involving soft tissues (muscle, skin) are more frequently reported. AH is diagnosed in patients without previous personal or family bleeding history in which prolonged activated partial thromboplastin time is not corrected after mixing and incubating for 2-4 hours at 37°C equal volumes of patient and normal plasma, FVIII:C levels are reduced and a specific FVIII inhibiting activity is detected and measured by the Bethesda assay or its Nijmegen modification. A prompt recognition of this life-threatening bleeding disorder and an early and aggressive treatment are mandatory, as diagnostic delays or inadequate treatments are associated with high mortality rates (up to 44% in literature). Therapeutic approach of AH is devoted to stop acute bleeds and to eradicate the FVIII autoantibody. Bleeding episodes can be treated with FVIII concentrates or desmopressin in patients with low titer inhibitors, but FVIII bypassing agents (activated prothrombin complex concentrates and recombinant activated FVIIa) are required for those with high-titer inhibitors or more severe bleeds. Steroids alone or in combination with cyclophosphamide are effective for eradicating autoantibodies in most cases. More recently, increasing evidence suggests a role for rituximab in this setting, in particular as a second-line approach.