Critical-care units can be barometers for appropriate antimicrobial use. There, life and death hang on empirical antimicrobial therapy for treatment of infectious diseases. With increasing therapeutic empiricism, triple-drug, broad-spectrum regimens are often necessary, but cannot be continued without fear of the double-edged sword: a life-saving intervention or loss of life following Clostridium difficile infection, infection from a resistant organism, nephrotoxicity, cardiac toxicity, and so on. While broadened initial empirical therapy is considered a standard, it must be necessary, dosed according to pharmacokinetic-pharmacodynamic principles, and stopped when no longer needed. Antimicrobial stewardship interventions shepherd these considerations in antimicrobial therapy. With pharmacists and physicians trained in infectious disease and critical care, clear-cut interventions can be focused on beginning or growing a stewardship program, or proposing future studies.