Apoptosis is a controlled form of cell death that allows the removal of cells during physiological or pathological processes. Recent studies suggested a potential link of apoptosis with processes leading to thrombophilia. In this review, we describe the mechanisms by which apoptotic cells would cause activation of blood coagulation and instability of atherosclerotic plaque leading to increased thrombus formation. A well-recognized acquired thrombophilia is the anti-phospholipid syndrome. Alterations of the phospholipid phase of cell membranes in the course of membrane blebbing, a characteristic morphological change occurring during the late apoptotic process, have been shown to be associated with the production of anti-phospholipid antibodies. These surface blebs on apoptotic cells have been shown to be the sites of enhanced procoagulant activity. Reversely, several anti-phospholipid antibodies may also induce apoptosis resulting in the formation of immunogenic and highly procoagulant surface blebs. Apoptosis was also found to be associated with increased cell surface tissue factor procoagulant activity, the so called tissue factor de-encryption. Atherosclerotic plaque rupture is associated with increased thrombus formation. Apoptotic inflammatory cells such as macrophages and T cells are abundant in atherosclerotic plaque and may be related to plaque instability. During the process of endothelial cell apoptosis, a loss of the anticoagulant property of endothelial cell surface concomitantly with an increase in their adhesiveness for leukocytes might probably occur. These changes may be important for the rapid progression of the atherosclerotic process.