Clinical management of von Willebrand disease (or von Willebrand disorder [vWD]) often involves factor replacement or desmopressin acetate (DDAVP) therapy to control (potential) bleeding. Laboratory monitoring involves testing patient samples prior to therapy and at discreet time points after therapy. Classical testing generally comprises assays for factor VIII:coagulant activity, von Willebrand factor (vWF):antigen and vWF:ristocetin cofactor activity. The PFA-100 (platelet function analyser) is a relatively new tool for the investigation of primary hemostasis, and studies have shown its potential utility in identifying both vWD and platelet disorders, and in monitoring DDAVP therapy in these patients. However, the PFA-100 has limited utility in monitoring factor replacement therapy. The collagen-binding activity (vWF:CB) assay is a relatively new functional vWF assay and studies have also shown its utility in identifying vWD, and in monitoring both DDAVP and factor replacement therapy in these patients. This review assesses the laboratory monitoring of therapy for vWD with a special focus on the combined potential utility of the PFA-100 and a vWF:CB assay sensitive for the presence or absence of large vWF multimers. This review should be of value to both hemostasis scientists and clinical specialists.