Operational research is increasingly being discussed at institutional meetings, donor forums, and scientific conferences, but limited published information exists on its role from a disease-control and programme perspective. We suggest a definition of operational research, clarify its relevance to infectious-disease control programmes, and describe some of the enabling factors and challenges for its integration into programme settings. Particularly in areas where the disease burden is high and resources and time are limited, investment in operational research and promotion of a culture of inquiry are needed so that health care can become more efficient. Thus, research capacity needs to be developed, specific resources allocated, and different stakeholders (academic institutions, national programme managers, and non-governmental organisations) brought together in promoting operational research.