Although active immunological killing is often the first thing that comes to mind when we think about host defense against infection, in some cases, the host can achieve better health outcomes by tolerating low-grade infection. The concept of tolerance originates in agriculture, describing crop strains that are able to deliver high yields while sustaining pathogen burdens that would severely compromise other strains. The same concept can be applied to animal defense against infection: tolerant hosts are able to maintain health and fitness despite infection. Whereas the mechanisms of immunological resistance to infection are typically based in immune responses that kill pathogens, mechanisms of tolerance could be wholly independent of immunological activity. They may include healing of pathogen-induced damage, metabolic compensation for the costs of infection, or other processes that alleviate the symptoms of infection without directly reducing pathogen burden. The evolutionary pressures on tolerance mechanisms can be substantially different than those on resistance mechanisms, and host-pathogen co-evolution is expected to unfold very differently when tolerance is a bigger factor than resistance. Although tolerance may be easy to conceptually describe, it is considerably more difficult to empirically quantify. Furthermore, tolerance and resistance mechanisms are often intertwined, with genetic or environmental variability simultaneously impacting both resistance and tolerance. As we study the physiological and immunological basis for total immune defense, our team is attentive to both tolerance and resistance phenotypes and mechanisms.