Guide to the primary therapy of WM. HV indicates hyperviscosity; cp, centipoise; BDR, bortezomib, dexamethasone, rituximab; CPR, cyclophosphamide, prednisone, rituximab; RCD, rituximab, cyclophosphamide, dexamethasone; VR, bortezomib, rituximab; FR, fludarabine, rituximab; and R, rituximab. (1) Because of potential risk of stem cell damage and/or secondary malignancies, may consider as an alternative option if other treatment choices are either unavailable or inappropriate for a particular patient. (2) Consider an attenuated schedule for fludarabine administration in patients with more indolent disease presentation. (3) Avoid as monotherapy in patients with hyperviscosity and with FcγRIIIA-158 F/F polymorphism. For rituximab-based therapies, consider maintenance rituximab in responding patients. Clinical trials should be considered for patients whenever possible.