This book was devoted to the latest advances achieved in the antibacterial field, with a focus on the recent efforts made to develop new antimicrobial agents with novel modes of action, and a perspective on future directions of this line of research. Antimicrobial resistance has become a major threat to global health, and the twenty-two published articles here reported put in evidence that the discovery and development of new antibiotics are extremely challenging. The antimicrobial research covers a wide area, spanning from the design of new compounds, also supported by molecular modeling techniques, their synthesis and characterization, and biological tests. In this context, the current crisis caused by the COVID-19 pandemic, but also older threats, such as the human immunodeficiency virus or the hepatitis C virus, require greater attention than ever. The research works described in this book provide an extremely useful example of the results achieved in the field of antibacterial drug development. The search for new chemical entities was approached starting from both natural and synthetic compounds and addressing different targets. In addition, recent findings were presented and discussed highlighting the strategies to fight bacterial resistance. Detailed references to the state-of-the-art can be found in this book. We strongly encourage the wide group of readers to explore the book that we are presenting, to get inspired to develop new approaches for the diagnosis and treatment of antibacterial diseases, and to circumvent resistance issues.