With the advent of reduced-intensity conditioning regimens and improvements in supportive care, hematopoietic cell transplantation (HCT) has become increasingly available to older adults and medically vulnerable populations with hematologic diseases. However, adverse outcomes including long-term treatment-related distress, disability (frailty), and death remain important concerns in this population. In other areas of oncology, comprehensive geriatric assessments have been used to stratify patients for treatment-related risk, and patient-reported outcomes (PROs) have helped in understanding treatment-related toxicity from a patient perspective. However, these powerful tools have not yet become widely used in HCT. Here, we review the theories and available data that support the development of pretreatment functional assessments and longitudinal PRO sampling in HCT. We discuss the potential for these techniques to improve transplantation outcomes through risk stratification, interventional studies, and predictive models that incorporate genetic and biomarker data. Predicting and understanding long-term transplantation-related toxicity through functional assessments and PROs will be critical to calculating the risk/benefit ratio of aggressive therapies in older patient populations, and we contend that functional assessments and PRO sampling should become standard parts of the routine evaluation of HCT patients.