The risk of healthcare-associated infections (HCAIs) in developing countries can exceed 25% compared to developed countries. Lack of awareness and institutional framework to deal with patient safety in general and HCAI in particular perpetuates the culture of acceptance of avoidable risks as inevitable. Most HCAIs are avoidable and can be prevented by relatively simple means. It is no longer acceptable to put patients at risk of avoidable infections. The World Health Organization (WHO)-led World Alliance for Patient Safety launched a worldwide campaign on patient safety focusing on simple means like hand hygiene to combat HCAIs. To drive necessary changes to deliver sustainable improvement in clinical care requires strategic approach and clinical leadership. This article reviews the scale of the problem, the WHO recommended interventions and improvement strategies in institutional setup in developing and transitional countries.