Bacteria are under constant predation from viruses, called bacteriophages (phages). This threat has driven the evolution of multiple defense systems, including the CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR associated genes) immune pathway. Phages are not passive bystanders in their CRISPR-mediated demise, however, as many have developed potent protein inhibitors of the bacterial adaptive immune system. Here, I review the work that led to the discovery of many distinct "anti-CRISPR" proteins. Furthermore, I outline how understanding their mechanisms of action has provided a suite of specific and high-affinity reagents to modulate and study CRISPR-Cas applications.