Quorum sensing (QS) is a cell density-dependent regulatory system that orchestrates the group behavior of unicellular organisms by synchronizing the expression of certain gene(s) within the clonal community of same species. Bacterial pathogens often employ QS system to establish efficiently an infection. A large part of low GC Gram-positive bacteria belonging to phylum Firmicutes use thiolactone/lactone peptides as communication signals so-called autoinducing peptides (AIPs) to coordinate QS circuit. In particular, QS of staphylococci, enterococci, and clostridia have been intensively studied in terms of alternative target of anti-pathogenic chemotherapy independent of bactericidal antibiotics. Thus far, a number of quorum quenching (QQ) agents that targeting the QS circuit of these Gram-positive pathogens have been developed by random screening of natural compounds or rationale design of AIP antagonists. This review summarizes those QQ agents and previews their potential as post-antibiotic drugs.