Timely provision of adequate antimicrobial coverage in an initial anti-infective treatment regimen results in optimal outcomes for bacterial and fungal infections. However, selection of appropriate antimicrobial regimens for treatment of infections in the intensive care unit (ICU) can be challenging due to expansion of resistance, which typically requires use of multidrug anti-infective regimens to provide adequate coverage of important pathogens commonly seen in the ICU setting. Indeed, a recent additional call to action by the Infectious Diseases Society of America (IDSA) has enforced the impact that antimicrobial-resistant pathogens can have on patient care. The term ESKAPE has been coined by this IDSA group to refer to Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species, the etiologic causes of the majority of hospital-acquired infections in the United States that are able to effectively "escape" our antibiotic arsenal and that also mandate discovery of new antimicrobial agents. This article reviews select antibacterial agents and an antifungal agent in late stages of clinical development that appear to have potential for treatment of infections in the ICU.