Atherosclerosis is the major cause of cardiovascular disease. Hypercholesterolaemia, hypertension and cigarette smoking are the common risk factors for atherosclerosis. These risk factors unite behind a convergence of mechanism, involving oxidation and inflammation in the artery wall that, with time, gives rise to characteristic fatty-fibrous lesions. Physical trauma and inflammation produce lesion rupture, which can lead to clinical events such as heart attack and stroke, or resolve with plaque growth. Disease progression is marked by the inflammatory indicator CRP (C-reactive protein). Early indicators of heart attack are the inflammatory marker CD40, and the cardiac myofilament protein troponin. Coronary atherosclerosis is the common cause of heart failure (HF). Disordered calcium signalling to the myofilaments occurs in HF and in cardiomyopathy. Enhanced calcium signalling suppresses HF. Neuro-humoral and biomechanical processes, as seen in hypertension, produce cardiac hypertrophy, which predisposes to HF through apoptosis. Although in humans cardiac damage produces permanent loss of cells, because the heart cannot regenerate, developments in stem cell technology suggest that help is at hand.