Cholesterol-dependent cytolysins (CDCs) are a large family of toxins expressed by many species of gram-positive pathogenic bacteria. Several new CDCs have recently been discovered in other related species. In addition to its cytolytic activity, many other new functions have been observed in the interaction between the host and the bacterium. Modulation and apoptosis of immune cells are prompted at sublytic concentrations. These toxins bind specifically to mammalian cell receptors, suggesting new host vigilant mechanisms to sense pathogenic bacteria. In this work, we review all these aspects in several genera of gram-positive bacteria.