Humans are changing the environmental conditions of our planet, and animal immune functions are being affected by these modifications. For instance, a diversity of chemical contaminants is entering ecosystems and modifying immune functions directly or indirectly through altered host–parasite interactions. Also, global temperature changes have caused outbreaks of disease that have decimated and even extirpated some host species, outcomes partially driven via immune alterations. Finally, some invasive species are immunologically distinct or impose stress on native species, factors that may facilitate the establishment of nonnative hosts as well as parasite transmission to native species. Here, we summarize the known and likely effects of pollutants, nonnative species introductions, and increases in ambient temperature on host immune functions and infections. We then identify future directions for research given our sparse knowledge of immune variation in natural populations. In sum, we advocate integrative, multidisciplinary work at diverse spatial and temporal scales to assess and prevent anthropogenic global changes from further compromising animal immune functions.