Insight into how the immune system recognizes and responds to pathogens had led to landmark advances in biology and medicine in the last decades. This year's Albert Lasker Award for Basic Medical Research honors Zhijian "James" Chen for the discovery of cGAS, the enzyme that senses foreign and "pathogenic" self-DNA-self-DNA aberrantly located in intracellular compartments. The definition of the cGAS-STING pathway opens new horizons for the understanding and treatment of human disease.