The lecture will begin by describing research on CRISPR systems containing single subunit Cas proteins and multi-subunit Cascade complexes with the emphasis on assembly, target recognition, cleavage autoimmunity and the impact of anti-CRIPR proteins in suppressing the CRISPR-Cas surveillance pathway. The lecture will next focus on multi-subunit type Ill CRISPR Csm complexes outlining mechanisms underlying target RNA binding and cleavage, as well as cyclic oligoadenylate (cOA) second messenger formation. Next, the lecture will address mechanistic insights into cOA-mediated activation of CARF­effector cassettes with the emphasis on effectors that are nucleases, transmembrane domains, deaminases and NADases, that trigger abortive infection. The lecture will end with a mechanistic description on some examples of recently identified bacterial systems involved in antiphage defense.