Atherosclerotic lesions can result in fatal cardiovascular disease, but what triggers the formation of the atheroma plaques and their progression still begs further investigation. In 'Bench to Bedside', Göran K Hansson and Lars Klareskog peruse how the NLRP3 inflammasome can be activated by cholesterol crystals and worsen atherosclerosis by triggering inflammation through the release of IL-1β from macrophages. But these cells can also die at the lesion site, forming a necrotic core in the atheroma by building up apoptotic cells and debris. In 'Bedside to Bench', Ira Tabas discusses a human study showing that lesional necrosis along with thinning of the fibrotic cap are predictive of culprit lesions involved in fatal disease. Understanding the molecular underpinnings of these two morphological features may lead to new therapies to prevent or decrease the risk for major cardiovascular disease.