The plasma membrane defines the boundary of every living cell, and its integrity is essential for life. The plasma membrane may, however, be challenged by mechanical stress or pore-forming proteins produced by the organism itself or invading pathogens. We will here review recent findings about pore-forming proteins from different organisms, highlighting their structural and functional similarities, and describe the mechanisms that lead to membrane repair, since remarkably, cells can repair breaches in their plasma membrane of up to 10,000 microm(2).