The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems are adaptive immunity mechanisms present in many archaea and bacteria. These systems consist of *cas* genes and unique spacers, with diverse architectures and high rates of evolution. This review provides an updated analysis of the evolutionary relationships between CRISPR-Cas systems and Cas proteins, delineating three major types and several subtypes. Given the complexity and dynamic evolution of these systems, a unified classification should integrate multiple criteria, including phylogenies of *cas* genes, sequence and organization of CRISPR repeats, and CRISPR-Cas locus architecture. The authors propose a 'polythetic' classification that combines these criteria. The review also discusses outstanding problems in CRISPR-Cas classification and nomenclature, emphasizing the need for continuous updates and revisions based on new sequence and structural data.The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems are adaptive immunity mechanisms present in many archaea and bacteria. These systems consist of *cas* genes and unique spacers, with diverse architectures and high rates of evolution. This review provides an updated analysis of the evolutionary relationships between CRISPR-Cas systems and Cas proteins, delineating three major types and several subtypes. Given the complexity and dynamic evolution of these systems, a unified classification should integrate multiple criteria, including phylogenies of *cas* genes, sequence and organization of CRISPR repeats, and CRISPR-Cas locus architecture. The authors propose a 'polythetic' classification that combines these criteria. The review also discusses outstanding problems in CRISPR-Cas classification and nomenclature, emphasizing the need for continuous updates and revisions based on new sequence and structural data.