Biobanking of atherosclerotic tissue samples has contributed to our understanding of vascular occlusive disease. The careful examination of atherosclerotic plaques derived during vascular surgery or autopsies helped shape our minds in understanding the underlying substrate of arterial thrombosis. This review will outline concepts of progression of atherosclerotic disease that have been based on descriptions of human plaque pathology. In addition, we will discuss the current shift in clinical presentation and underlying pathology of acute cerebral and coronary events that asks for a careful consideration of the currently widely applied description of the "vulnerable plaque". The shift in atherosclerotic plaque characteristics that associate with a thrombotic event reflects the treatment and risk factor management that has undergone major changes in recent times. These changes may influence the value of past biobanking efforts in the current era: many inferences are being made upon sample data from cohorts that have been assembled in previous decades while large shifts in patient demographics and disease substrates over time occurred raises the question if biomarkers validated in historical biobanks can be extrapolated to the current era. As an example of altering profiles of biomarkers in the last decade, a panel of twelve selected plasma proteins was measured in the Athero-express cohort, showing time-dependent trends in serum biomarkers over the last decade. These findings strengthen our hypothesis that the pathogenesis of cardiovascular disease (CVD) is changing and future biobanking is required to successfully keep track of the mechanisms involved in CVD pathogenesis today.