Type IV secretion systems (T4SSs) are versatile multiprotein nanomachines spanning the entire bacterial cell envelope in Gram-negative and Gram-positive bacteria. They play important roles through the contact-dependent secretion of effector molecules into eukaryotic hosts and conjugative transfer of mobile DNA elements as well as contact-independent exchange of DNA with the extracellular milieu (Grohmann et al., 2018). T4SSs from Gram-negative bacteria have been studied in much more detail, but insights on mechanistic details of T4SSs from Gram-positive bacteria are growing rapidly underlining the importance of these nanomachines in the thick-walled Gram-positives. These nanomachines have been found in a wide variety of Gram-positive bacteria, encoded both on conjugative plasmids, Integrative and Conjugative Elements (ICEs) and on pathogenicity/genomic islands. The talk will include the most prominent ones. Then I will focus on two prototypes, the one encoded by the broad-host-range Enterococcus/Streptococcus plasmid pIP501 studied by our group and that of the sex-pheromone-responsive Enterococcus faecalis plasmid pCF10.