The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.