Bacteria have had a fundamental impact on vertebrate evolution not only by affecting the evolution of the immune system, but also generating complex interactions with behavior and physiology. Advances in molecular techniques have started to reveal the intricate ways in which bacteria and vertebrates have coevolved. Here, we focus on birds as an example system for understanding the fundamental impact bacteria have had on the evolution of avian immune defenses, behavior, physiology, reproduction and life histories. The avian egg has multiple characteristics that have evolved to enable effective defense against pathogenic attack. Microbial risk of pathogenic infection is hypothesized to vary with life stage, with early life risk being maximal at either hatching or fledging. For adult birds, microbial infection risk is also proposed to vary with habitat and life stage, with molt inducing a period of increased vulnerability. Bacteria not only play an important role in shaping the immune system as well as trade-offs with other physiological systems, but also for determining digestive efficiency and nutrient uptake. The relevance of avian microbiomes for avian ecology, physiology and behavior is highly topical and will likely impact on our understanding of avian welfare, conservation, captive breeding as well as for our understanding of the nature of host-microbe coevolution.