A new study identifies a wide array of previously unknown molecular functions and enzymatic activities microbes use to protect against viral threats. While the results break new ground in the understanding of the adaptive arms race between phages and their prokaryotic hosts, they could also inform the development of molecular technologies, like CRISPR-Cas, which could lead to new tools for gene manipulation, molecular detection and targeted cell destruction, for example. The viruses that prey upon bacteria and archaea are perhaps the most diverse and abundant biological entities on Earth. Viruses have evolved a diverse set of strategies to counteract many prokaryotic defense systems. Given the vast breadth of bacteriophages and archaeal viruses and their well-known ability to evade host immunity through complex co-evolutionary strategies, it's expected that a similar mélange of adaptive immune defenses against viral attacks also exist. However, according to the authors, only a relative few are known. Here, Linyi Gao and colleagues bioinformatically predicted defense genes in most available prokaryotic genomes. Further experimental testing revealed 29 widespread novel defense mechanisms collectively present in nearly one-third of all sequenced prokaryote genomes, which likely mediate antiviral protection against specific viruses. According to Gao et al., many of these mechanisms make use of enzymes not known to be associated with antiviral activities. The results have broad implications for understanding antiviral resistance and host-virus interactions in natural populations of microbes, as well as for advancing technological applications.