Many factors may influence the level of compliance with hand hygiene recommendations by healthcare workers. Lack of products and facilities as well as their inappropriate and non-ergonomic location represent important barriers. Targeted actions aimed at making hand hygiene practices feasible during healthcare delivery by ensuring that the necessary infrastructure is in place, defined as 'system change', are essential to improve hand hygiene in healthcare. In particular, access to alcohol-based hand rubs (AHRs) enables appropriate and timely hand hygiene performance at the point of care. The feasibility and impact of system change within multi-modal strategies have been demonstrated both at institutional level and on a large scale. The introduction of AHRs overcomes some important barriers to best hand hygiene practices and is associated with higher compliance, especially when integrated within multi-modal strategies. Several studies demonstrated the association between AHR consumption and reduction in healthcare-associated infection, in particular, meticillin-resistant Staphylococcus aureus bacteraemia. Recent reports demonstrate the feasibility and success of system change implementation on a large scale. The World Health Organization and other investigators have reported the challenges and encouraging results of implementing hand hygiene improvement strategies, including AHR introduction, in settings with limited resources. This review summarizes the available evidence demonstrating the need for system change and its importance within multi-modal hand hygiene improvement strategies. This topic is also discussed in a global perspective and highlights some controversial issues.