From a microbe's point of view, our bodies are excellent places to live and as a result we are covered with microorganisms. Most of these associations are benign or even beneficial, but a few are damaging to the animal host and they would rapidly spread throughout our tissues if it were not for the immune system. This intricate and complex collection of proteins, cells and tissues has the daunting task of keeping the tens of billions of little travelers attached to our bodies from entering areas where they ought not to be. It is nearly unbelievable that the immune system is up to the task, yet it certainly is and our lives depend on it. This chapter will describe the array of defenses that mammals have to protect themselves from infectious disease.