This chapter surveys the methods that can be used for the synthesis of phosphonium salts. A special attention is dedicated to the synthesis of tetraarylphosphonium salts that are, from a synthetic point of view, less accessible than other series of phosphonium salts (e.g. tetraalkyl, triarylalkyl phosphonium salts). The chapter reports the use of phosphonium as a tool for organic synthesis and the use of phosphonium salts as ionic liquids (ILs), as phase transfer catalyst (PTC) and chiral PTC, and finally as a tool for peptide coupling. It discusses the biological applications of phosphonium salts. The use of phosphonium salts for the targeting of mitochondria is addressed and the use of phosphonium-based amphiphilic compounds for nucleic acid delivery and as a bactericidal agent is surveyed. Some examples dedicated to the use of phosphonium salts for nucleic acid delivery and as bactericidal agents are presented. 2.1 Introduction 2.2 Synthesis of Phosphonium Salts 2.3 Phosphonium Salts as a Tool for Organic Synthesis 2.4 Phosphonium Salts for Biological and Medical Applications 2.5 Conclusion