Platelets may selectively execute apoptosis (PL-Apo), activation (PL-Act), and both or no responses when exposed to different chemical agents, shear stresses, and stored under blood banking conditions. Appropriate diagnosis of PL-Apo is an important issue of platelet physiology investigations. However, in diagnosing PL-Apo, there is a risk of a false-negative or false-positive diagnosis. The goal of the current review is to present recommendations that may help to avoid incorrect PL-Apo diagnosis. Analyzing reported studies, we recommend (1) using platelet-rich plasma rather than isolated platelets to minimize artificial stimulation of PL-Apo during platelet isolation, (2) using established optimal conditions for stimulation of PL-Apo and/or PL-Act, (3) using a panel of PL-Apo and PL-Act markers, and (4) appropriate positive and negative controls for quantification of PL-Apo and PL-Act responses. [ABSTRACT FROM AUTHOR]