Heart disease is one of the leading causes of death worldwide. Markers are needed for the diagnosis, prognosis, therapeutic monitoring and risk stratification of heart attacks and chronic heart failure. The procedure for biomarker development involves many steps from the discovery of the marker, to the validation of the marker, and finally to the incorporation into clinical practice. The methods developed for the biomarker discovery in the blood for heart disease will be used for less common disease such as childhood cancer, where samples are scarce. We have used label-free relative protein quantification using mass spectrometry (LC/MS/MS) to obtain the global protein profiles of patients with coronary artery disease. We applied this approach to 250 samples selected from a consecutive series of 3500 patients that underwent coronary angiography at the German Heart Center in Munich. Our study provides the most comprehensive dataset of protein changes in patients with coronary artery disease described so far. We demonstrated that moderately abundant proteins can be used for risk classification in coronary artery disease. Currently we are analyzing the metabolites in the serum of these patients.