Blood handling devices such as left ventricular assist devices and total artificial hearts offer life-saving treatments for patients suffering from severe heart failure. Current devices have clinically proven that heart assist pumps are a safe and effective therapy, and indeed in many cases they are the only available method of treatment. However, current devices cause side effects including stroke, bleeding, infection, and thrombosis, preventing the technology from reaching its full potential. If the side effects could be reduced, then more patients could benefit from these devices. The complications are related to damage to blood cells and proteins as a result of contact with foreign materials and mechanical stress. There is a need for better devices with minimal blood impact to enable more patients to be safely treated; better tools, especially flow cytometry, could support the device development life cycle. In this chapter we review the clinical, in vivo, and in vitro flow cytometry data available for ventricular assist devices, conduct a gap analysis, and identify areas of future possibilities for device developers to establish new flow cytometry-based methodologies.