Inflammation is an integral part of animal biology. It provides critical protection from adverse environmental factors by enforcing the defense of homeostasis and the functional and structural integrity of tissues and organs. Recent advances have uncovered a broad range of biological processes that involve inflammatory control, calling for a renewed framework of inflammation beyond its classical roles in defense from infection and injury. In this Review, new perspectives on inflammation biology are discussed and new research directions are suggested to address the fundamental gaps in our current understanding.