The CRISPR–Cas system is an archaeal and bacterial adaptive immune system that provides sequence-specific defence against foreign nucleic acids. Whereas type I and type II systems recognize and cleave double-stranded DNA, the type III complex (known as Cmr) targets single-stranded RNA (ssRNA), and comprises six proteins and a CRISPR RNA (crRNA) that is complementary to target ssRNAs. Taylor et al. used cryo-electron microscopy to solve the structure of the intact Cmr complex of Thermus thermophilus in both the absence and presence of a target ssRNA. The structures showed that the Cmr–crRNA complex adopts a capsule-like structure with a double-helical core comprising Cmr4 and Cmr5 subunits capped by Cmr2–Cmr3 and Cmr1–Cmr6 heterodimers. Following binding to ssRNA, the complex undergoes conformational changes to accommodate the crRNA–target ssRNA duplex, and the thumb-like β-hairpin domains of Cmr4 intercalate between segments of the duplex, which facilitates target cleavage at six nucleotide intervals.