Targeting virulence factors has gained increasing attention as a potential approach to new antibiotics. Small molecule inhibitors of virulence have been shown to change the course of disease in whole organism infection models. Recently, key advances in the field include the identification of novel targets within cell signaling pathways, a new class of anti-virulence compounds that target bacterial defenses against host immunity, and a growing body of in vivo data to support the general approach of anti-virulence therapies. Additionally, there has been a distinct trend toward developing broader spectrum anti-virulence compounds, in particular agents with activity against diverse Gram-negative organisms. Herein we provide an update on the status of the field with a focus on recent advancements.