The connection between homocysteine and thrombosis was identified approximately 25 years ago when it was reported that people with a rare condition called homocystinuria accumulated homocysteine in the blood and excreted it in the urine. Recent studies provide overriding evidence to suggest that elevated blood homocysteine levels can cause thrombosis and some 10-20% of coronary heart disease cases have been linked to elevated homocysteine levels. Factors such as hereditary predisposition, ethnic origin, gender, age and diet affect homocysteine level but the mechanisms by which homocysteine causes thrombosis are largely unknown. Further information on the mechanisms involved has emerged in the last few years and this essay elucidates these developments.