Zheng et al. have conducted a systematic mixed review of published literature to explore the role of spirituality in patients undergoing hematopoietic cell transplantation (HCT).1 Patients with different malignant and non-malignant conditions undergo HCT, often with a curative intent. HCT is an intensive procedure requiring close monitoring and appropriate management of complications. While prior research has focused on identifying the role of traditional medical factors such as age, disease type, risk status, and genetic/molecular abnormalities as determinants of outcomes, less is known about the role of other sociobiological or non-biological factors affecting HCT outcomes. Patient-reported quality of life (QOL) is increasingly recognized as an important domain influencing cancer recovery, including HCT recipients.2 In this context, patients’ spiritual beliefs and their management during HCT setting could potentially influence the patient’s well-being and QOL. Spirituality likely has biological implications that could impact HCT outcomes.3 Interestingly, recent data has begun to identify complex genomic mechanisms that could explain similar socioenvironmental influences of QOL on HCT outcomes.4, 5 In the current study, Zheng et al. have included 35 studies describing the perceptions and spiritual needs of patients during HCT. They noted that patients’ spiritual dependence increased during HCT irrespective of underlying religious beliefs. In addition, the spiritual needs varied significantly and were affected by several factors including education, ethnicity, and culture. While most patients seem to have increased spiritual dependence during HCT, the data is too heterogeneous to support definitive conclusions. More definitive clinical trials in the peri-HCT setting are needed to consistently investigate this aspect of patient need and QOL as well as investigate methods for addressing these needs. However, the current review is an important step in advancing the exploration of spiritual needs of the patients during HCT and hopefully integrating this with patient-reported outcomes. Future research efforts should focus not only on the effect of spirituality on HCT outcomes but also on the biologic and genomic mechanisms potentially mediating such a relationship.