Abstract Background: Hospital-acquired infections (HAIs) are a persistent concern and include surgical site infections, intravascular line-associated infections, pneumonia, catheter-associated urinary tract infections, and C. difficile infection. Method: Review of the pertinent English-language literature. Results: Hospital-acquired infections result in significant increases in morbidity, mortality rates, and cost and are a focus of efforts at reduction. Conclusion: I discuss efforts specific to each of the most common infections and a philosophical approach to prevention that strives to achieve zero potentially preventable hospital-acquired infections.