Nosocomial infection or ‘healthcare-associated infection’ (HAI), is one of the most common medical complications affecting patients in intensive care units (ICUs). The prevalence of HAI generally exceeds 25% in ICUs worldwide and ICU-acquired HAI accounts for more than 20% of all HAI in general. HAI depends on the patient’s underlying disease, the presence of invasive devices, use of antimicrobial therapy, type of ICU, and workload and training of healthcare workers. Surveillance has a major impact on the incidence of infections. HAI rates are used to assess patient safety and healthcare systems’ effectiveness, but adjustment for case-mix and standardization of surveillance method are needed. Prevention must be guided by the measurement of indicators, such as HAI rates, structure indicators, process indicators, and audits using checklists to assess if correct procedures and equipment are in place. Routine hand hygiene is the most important feature of infection control. Although the optimal approach to reducing HAI in critically-ill patients remains unclear, recent studies and large quality improvement initiatives have shown that education-based strategies with multimodal interventions, including some bundle approaches, can decrease HAI rates in ICUs.