ABSTRACT Gram-negative pathogens are a rapidly increasing threat to human health worldwide due to high rates of antibiotic resistance and the lack of development of novel antibiotics. The protective cell envelope of gram-negative bacteria is a major permeability barrier that contributes to the problem by restricting the uptake of antibiotics. On the other hand, its unique architecture also makes it a suitable target for antibiotic interference. In particular, essential multiprotein machines that are required for biogenesis of the outer membrane have attracted attention in antibacterial design strategies. Recently, significant progress has been made in the development of inhibitors of the β-barrel assembly machine (BAM) complex. Here, we summarize the current state of drug development efforts targeting the BAM complex in pursuit of new antibiotics.