Recent technological advances have seen increasing numbers of complex structures from diverse pore-forming toxins (PFT). The ClyA family of α-PFTs comprises a broad variety of assemblies including single-, two- and three-component toxin systems. With crystal structures available for soluble subunits of all major groups in this extended protein family, efforts now focus on obtaining molecular insights into physiological pore formation. This review provides an up-to-date discussion on common and divergent structural and functional traits that distinguish the various ClyA family PFTs. Open questions of this research topic are outlined and discussed.