Comparative-genomic predictions validated by a rapidly growing body of experimental results indicate that the CRISPR-Cas is an adaptive immunity system that is widely employed by archaea and bacteria for defense against diverse invading elements, in particular, viruses. The system functions by integrating fragments of alien element genes into CRISPR loci and employing the resulting spacers, after transcription and processing, as guide RNAs to abrogate the replication of the cognate elements by cleaving nucleic acid molecules complementary to the guide. In some cases, at least, the target of CRISPR-Cas is the genomic DNA of an invading genetic element. Experiments aimed at molecular dissection of CASS proved the predicted principle of its action and are starting to reveal multiple activities of the protein components of CASS and the molecular architecture of complexes formed by these proteins. However, an enormous amount of experimental work remains to be done to elucidate the mechanisms of CASS, in particular, the molecular details of spacer incorporation into the CRISPR loci and the specific pathways of RNA-guided destruction of alien genomes. These experiments can be expected to reveal the considerable mechanistic diversity that reflects the extreme diversity of cas gene repertoires and operonic organization. Another important direction of future work is the characterization of the arms race between CRISPR-Cas and viruses of prokaryotes and elucidation of putative mechanisms of counterdefense employed by the viruses. Finally, it is worth noting that, by integrating fragments of invaders' genomes into the genomes of the archaeal and bacterial hosts, the CASS effectively operates via a Lamarckian-type inheritance of acquired characters.