Hematopoietic stem cell transplantation (HSCT) is a rigorous therapy that carries significant risk of morbidity and mortality to individuals with hematologic malignancies undergoing this treatment. While relationships between psychosocial factors, immune function, and clinical outcomes have been documented in other cancer populations, similar studies of cancer patients undergoing HSCT have not yet been conducted. The clinical significance of these relationships may be particularly salient in this population given the critical role of a timely immune recovery and optimal immune regulation in preventing infections, mitigating risk for graft-versus-host disease, and eliminating malignant cells, thereby reducing morbidity and mortality. Evidence for the potential role of biobehavioral processes following HSCT is reviewed, mechanisms by which psychosocial factors may influence immune processes relevant to post-transplant outcomes are discussed, and a framework to ground future psychoneuroimmunology (PNI) research in this area is provided. The review suggests that the recovery period following HSCT may provide a “window of opportunity” during which interventions targeting stress-related behavioral factors can influence the survival, health, and well-being of HSCT recipients.