The inclusion of fungi in recent human and animal microbiome studies has revealed that microbiome features associated with health or disease are not exclusively bacterial. Factors known to impact bacterial microbiome development, such as gestational age at birth, breast feeding status and antibiotics also impact the mycobiome. Strong inter-kingdom interactions take place in the luminal gut, and while the mycobiome exhibits increased inter-individual variability, certain fungi are stable colonizers. Here, we review recent studies showing that the gut mycobiome also plays an important role in disease states related to host immunity and energy metabolism. Some persistent species, such as Candida sp., as well as other less stable colonizers have been shown to play an important role in host-mycobiome immune cross talk. Mechanisms by which gut fungi interact with immune development have begun to be elucidated yet the majority remain elusive. Further investigation into these immune and metabolic mechanisms hold great potential for novel discoveries and will provided a much needed multi-kingdom understanding of the microbiome's influence on host health.