This chapter discusses the molecular mechanisms involved in colicin translocation across the outer membrane, the insertion of pore-forming colicins into the inner membrane and the inhibition of their lethal activities by the corresponding specific immunity proteins. The chapter focuses on colicin A, that the immunity protein interacts with the pore-forming domain of the colicin as it inserts into the inner membrane and that it prevents it from opening its channel as normally in the presence of membrane potential. The transmembrane helices of the immunity protein might somehow interact with membrane inserted portions of the colicin A channel in order to block any further conformational changes necessary for the channel opening. The chapter discusses the mode of action of colicin that is divided into three steps. They first bind to a specific receptor at the cell surface. For that purpose, some colicins have parasitized proteins of the outer membrane whose function is dedicated to the transport of iron siderophores (FepA, FhuA, FhuE, and Cir), of vitamin B12 (BtuB), or nucleotides (Tsx). Others have parasitized the major porin OmpF through which small hydrophilic solutes with MW of up to 650 Daltons.