Waldenström macroglobulinemia (WM) is a distinct indolent B-cell lymphoproliferative malignancy characterized by IgM paraproteinemia. Although the disease is sensitive to chemo-immunotherapy, it remains incurable and affected patients have a median survival of 5-10 years. Risk stratification in newly diagnosed patients should start with a prognostic evaluation based on the International Prognostic Scoring System for WM (IPSSWM) to identify those patients in whom particularly poor survival with chemotherapy is expected and in whom alternative treatment strategies, such as hematopoietic cell transplantation (HCT), should be considered. High-dose chemotherapy followed by autologous HCT (auto-HCT) results in disease-free survival of 45-65% at 5 years, but is unlikely to be curative. Chemosensitive disease at the time of auto-HCT is the most important prognostic factor for response rate and overall survival. Allogeneic donor HCT may offer a unique immune-mediated GVL effect with a plateau in relapse rates and potential for extended disease-free survival. The risk of allogeneic HCT complications is justified in HCT-eligible patients whose expected survival is <5 years. Here, we present the advances in non-transplant strategies and the therapeutic role of transplant, and suggest a treatment algorithm for selecting a HCT strategy while adhering to current evidence supporting autologous and allogeneic donor HCT for WM.