Healthcare-associated infections (HAIs) are a pressing and imminent patient safety concern as they cause substantial preventable morbidity and mortality. Despite this, there is a strong tendency for healthcare administrators and providers to view them as far less of a threat to patient safety than adverse events such as medication administration errors and falls. Further, validated strategies to prevent HAIs are frequently slow to be adopted. This paper reviews two HAIs of increasing visibility and importance - namely, methicillin-resistant Staphylococcus aureus and Clostridium difficile - and discusses the pivotal importance of hand hygiene and environmental cleaning in their prevention. Possible reasons why HAIs are approached differently from other patient safety issues are discussed, including the false sense of security created by the advent of antibiotics, the lack of randomized controlled trials supporting infection-control interventions and the systemic multifactorial causes of HAIs that result in a need for interventions that go far beyond traditional clinical boundaries. Suggested strategies to improve patient safety with respect to HAIs are provided, including a focus on the role of potential links to accreditation; the role of public reporting; healthcare facility design; change management strategies; visible leadership and role modelling; collaboration between facilities and with public health; reducing hospital overcrowding; and accountability and funding. Finally, the impact of the burgeoning interest of the media, the threat of legal liability and the well-being of healthcare providers are discussed.