Allogeneic hematopoietic stem cell transplantation is often the preferred treatment for patients with hematopoietic malignancies, affording them the best chance for long-term disease-free survival. Because related donors are the preferred source of hematopoietic stem/progenitor cells, consideration of familial predisposition to cancer should become standardized as part of pre-transplant assessments. Based on numerous published cases of poor outcomes for both the donor and recipient when allogeneic donors with deleterious germline variants in RUNX1 or CEBPA have been used for hematopoietic stem cell transplantation, such donors should be avoided. However, data do not exist for many other genes, which presents challenges to providers who are counseling patients and potential donors about risk. Hopefully, ongoing studies will fill these gaps and inform recommendations regarding suitability of universal donor screening in the future.