This chapter describes the dual role of bacteria-encoded proteins along with their impact on the bacteriophage biology and the repercussion in bacterial pathogenicity. The use of bacteriophage-encoded proteins as de-repressor proteins is an elegant strategy that allows the Staphylococcus aureus pathogenicity islands (SaPI) to be induced only when the helper phage has entered the lytic cycle. The chapter examines the dual role of various well-known and well-characterized bacteriophage moonlighting proteins and their impact on bacterial pathogenicity. The first example of moonlighting proteins studied was the homing endonuclease T4 I-TevI encoded by the T4 bacteriophage. This homing endonuclease, in addition to its main cleavage activity, has a role as a transcriptional regulator controlling its own transfer. Understanding the biology of bacteriophages is of great importance due to their crucial role in bacterial pathogenicity, as well as for the study of the different proteins and functions that they have for their own biology.