This paper explores the implications of building design for the management of cross infection in cystic fibrosis (CF) clinics, and the experiences of patients and staff. It is recommended that people with CF are segregated from one another, due to the risks of cross infection. This presents specific design challenges. We explore these issues drawing on data from an ongoing Arts and Humanities Research Council (AHRC) funded study ‘Pathways, Practices and Architectures’ (PARC). The study centres on three in-depth case studies of UK CF outpatient clinics, using qualitative methods including interviews, graphic maps, walk arounds, and observations, to examine the perspectives of patients, clinical staff, estates and facilities managers, and architects. Areas of CF clinics and hospital buildings identified as potential cross infection hot spots include: lifts; toilets; entrances and exits; waiting areas; narrow corridors; poorly ventilated clinic rooms. Suggestions for potential design improvements include: a one way ‘flow’, with separate entrances and exits; more clinic rooms; air filtration in outpatient clinic rooms; better availability of clinical waste bins and sluices. The paper also explores good practice examples where estates departments and architects worked collaboratively with users to redesign CF inpatient facilities, including full refurbishments, and smaller ‘work around’ adaptations. However, this is more challenging in shared outpatients’ departments, which are shaped by competing requirements of different clinics and user groups, and staff and patients expressed a desire for a dedicated CF clinic space. As practices of segregation in CF clinics are constantly evolving, there is also a need for buildings to be flexible and adaptable. Yet potential for change is restricted by limited resources and the design of existing building stock.