Infected organisms can resist or tolerate infection, with tolerance of infection defined as minimizing per-parasite reductions in fitness. Although tolerance is well studied in plants, researchers have only begun to probe the mechanisms and transmission consequences of tolerance in animals. Here we suggest that research on tolerance in animals would benefit from explicitly incorporating behavior as a component of tolerance, given the importance of behavior for host fitness and parasite transmission. We propose two distinct manifestations of tolerance in animals: tissue-specific tolerance, which minimizes fitness losses due to tissue damage during infection, and behavioral tolerance, which minimizes fitness losses by maintaining normal, fitness-enhancing behaviors during infection. Here we briefly review one set of potential immune mechanisms underlying both responses in vertebrate animals: inflammation and its associated signaling molecules. Inflammatory responses, including broadly effective resistance mechanisms like the production of reactive oxygen species, can incur severe costs in terms of damage to a host's own tissues, thereby reducing tissue-specific tolerance. In addition, signaling molecules involved in these responses facilitate stereotypical behavioral changes during infection, which include lethargy and anorexia, reducing normal behaviors and behavioral tolerance. We consider how tissue-specific and behavioral tolerance may vary independently or in conjunction and outline potential consequences of such covariation for the transmission of infectious diseases. We put forward the distinction between tissue-specific and behavioral tolerance not as a definitive framework, but to help stimulate and broaden future research by considering animal behavior as intimately linked to the mechanisms and consequences of tolerance in animals.