There is a long-standing evolutionary battle between viruses and their hosts that continues to be waged. The evidence of this conflict can be found on both sides, with the human immune system being responsive to new viral challenges and viruses having developed often sophisticated countermeasures. The “arms race” between viruses and hosts can be thought as an example of the “Red Queen” race, an evolutionary hypothesis inspired from the dialogue of Alice with the Red Queen in Lewis Carroll’s “Through the Looking-Glass”. At the same time, viruses have a minimal genomic content as they have evolved to hitchhike biological machinery of their hosts (or other co-infecting viruses). The minimalistic viral genome could be thought as the result of a “Black Queen” evolution, a theory inspired from the card game Heart, where the winner is the one with the fewest points at the end. The effects of this arms race are evident in the evolution of the human immune system. This system is capable of responding to diverse viral challenges, utilizing both the ancient innate immune system and the more recently evolved adaptive immune system of jawed vertebrates. It is now well-known that the two systems are linked, with innate immunity hypothesized to have provided raw material for the emergence of the adaptive immune response. The adaptive immune response comprises several protein families (including B and T cell receptors, MHC and KIR proteins, for example) that are encoded by complex and variable genomic regions. This complexity enables for responsive genetic changes to occur in immune cells, such as the ability of genomic hypervariable regions in B cells to recombine in order to produce more specific antibodies. Indeed, the human immune system is thought to be continually evolving via various mechanisms such as changes in the genes encoding immune receptors and the regulatory sequences that control their expression. For example, there is some evidence that exogenous viral infections can alter the expression of endogenous retroviruses, some of which contribute to the immune response. Viral countermeasures can include encoding decoy receptors for the signalling molecules of the immune response, altering the gene expression of adaptive immune cells during chronic infection or using host enzymes to facilitate viral immune escape. As the articles herein show, the immune system continues to be challenged by viral infections and these challenges continue to shape how the immune system combats pathogens, thus viruses and human immunity are continuously part of “Red and Black Queen” evolutionary dynamics. We had the pleasure of working with Jonas Blomberg as a reviewer during the course of the Research Topic and his untimely passing was a great loss. Prof. Blomberg made significant contributions, including to the nomenclature of endogenous retroviruses (ERVs), the evolution and characterization of specific human ERV (HERV) and the contribution of ERVs to diseases such as cancer. It is with great respect for his contributions to the ERV field that we dedicate this eBook to his memory.