Background: Directed blood donation is defined as the donation of blood or its components for the purpose of transfusion into a specified individual. Directed blood donation holds historic significance, and although practices as of 2021 encourage voluntary, nonrenumerated blood donations, public interest in directed donation remains. Requests to discuss the risks and benefits of directed donations are a common inquiry for transfusion medicine, transplant, and hematology/oncology professionals. This narrative review discusses the history of directed donation and summarizes directed donation considerations in the context of modern transfusion practices. Methods: We conducted a systematic search of PubMed for published literature on the topic of directed blood donation and gathered information about its benefits and potential harms with respect to the variety of products used in transfusion medicine. Results: The drawbacks of directed donation include transfusion-transmitted infection risk, alloimmunization risk, increased transfusion-associated graft vs host disease risk, decreased expediency in treatment, and increased administrative burdens. However, a role remains for directed blood donation in specific patient populations, such as individuals with rare blood types or immunoglobulin A deficiencies, because of the difficulties in finding compatible blood for transfusion. Conclusion: Clinicians should consider the risks and benefits when discussing directed blood donations with patients and family members.