Donated blood can be broken down into blood components for use in patient care. This article focuses primarily on packed red blood cells (PRBCs), as they experience breakdown during storage that may adversely impact patient outcomes. Patients require PRBC transfusions for a number of clinical reasons. Although transfusions of PRBCs provide some clinical benefit, they are also associated with increased morbidity and mortality across multiple patient populations, albeit the mechanisms underlying this relationship remain unclear. With an aging, more acutely ill population requiring aggressive treatment and a lack of transfusion alternatives, research focused on PRBCs has gained momentum. Proper interpretation of research findings on the part of clinicians depends on accurate data collection that includes aspects of both the transfused blood components and the recipients. The purpose of this article is to examine stored PRBC factors, blood-donor characteristics, transfusion-specific factors, and patient-specific characteristics as they relate to patient outcomes research. Challenges associated with performing and interpreting outcomes of transfusion-related research are presented. Implications of current evidence for patient care, such as awareness of benefits as well as risks associated with blood component transfusion, are also provided.