Despite impressive therapeutic progresses in the battle against infections, microorganisms are still a threat to mankind. With hundreds of antibacterial molecules, major concerns remain about the emergence of resistant and multidrug-resistant pathogens. On the other hand, the antiviral drug armamentarium is comprised of only a few dozens of compounds which are highly pathogen specific, and resistance is also a concern. According to Arturo Casadevall (Albert Einstein College of Medicine, NY, USA), we have now entered the third era of anti-infective strategy, which intends to favor the interplay between active molecules and the immune system. The first part of this review focuses on the potential immunomodulating properties of anti-infective agents, beginning with antibacterial and antiviral agents.