Inflammation plays a crucial pathophysiological role in the entire continuum of the atherosclerotic process, from its initiation, progression, and plaque destabilization leading ultimately to an acute coronary event. Furthermore, once the clinical event has occurred, inflammation also influences the left ventricular remodelling process. Under the same paradigm, there is evidence that lymphocytes play an important role in the modulation of the inflammatory response at every level of the atherosclerotic process. Low lymphocyte count (LLC) is a common finding during the systemic inflammatory response, and clinical and animal studies suggest that LCC plays a putative role in accelerated atherosclerosis. For instance, there is recent evidence that LLC is associated with worse outcomes in patients with heart failure, chronic ischemic heart disease and acute coronary syndromes. Further indirect evidence supports the pathologic role of LLC related to the fact that 1) lymphopenia--due to a decreased count of lymphocyte T cells--normally occurs as a part of the human ageing process, and 2) increased incidence of cardiovascular events has been reported in conditions where lymphopenia is common, such as renal transplant recipients, human immunodeficiency virus infection, survivors of nuclear disasters and autoimmune diseases. The aim of the present article is to review: a) the pathophysiological mechanisms that have been proposed for the observed association between LLC and cardiovascular diseases (CVD), b) the available evidence regarding the diagnostic and prognostic role attributable to LLC in patients with CVD, and; c) the potential therapeutic implications of these findings.