This editorial summarizes and discusses the themes of eleven articles (five reviews and six original studies) published in the Special Issue “Molecular Research On Platelet Activity in Health and Disease”. They give an international picture of the up-to-date understanding of (i) platelet signalling under physiological and pathological conditions, (ii) novel technologies for monitoring platelet functions and (iii) clinical applications of platelet-based-therapy for management of pathological conditions, not directly related to haemostasis and thrombosis.