Hematopoietic stem cell transplant (HSCT) patients can present a number of nutrition challenges despite recent advancements in medical care. Several areas of controversy exist, including whether probiotics can be safely used; the use of probiotics continues to expand but efficacy and safety is a concern in immunocompromised patients, including HSCT recipients. Second, parenteral nutrition continues to be the primary avenue for nutrition support despite growing evidence that enteral feedings can be successfully administered. Last, tight glycemic control has been associated with positive clinical outcomes in hospitalized patients. However, whether tight glycemic control can be achieved and is of benefit in this patient population continues to be debated. This article will discuss the current challenges facing clinicians regarding these 3 issues—probiotics, enteral nutrition support, and glycemic control—and future directions in HSCT.