Live cell imaging of immune cells in their natural in vivo environment can often unveil novel unexpected biology. We use mouse model systems to study how the innate immune system integrates into complex tissues and maintains homeostasis. We also study how perturbations can induce massive changes in the immune system that can lead to either a return to homeostasis or down a path of chronic disease. I will use the liver and peritoneal cavity macrophages to highlight how important these cells are to the local environment and how under some conditions the system is hijacked to the benefit of invaders.