Currently 15,000 to 16,000 people with HIV/AIDS are living in Switzerland. Many of these patients suffer from diverse signs and symptoms. One of the most common symptoms reported in the literature is fatigue with a rate ranging from 20 to 74%. It is well known that fatigue impacts negatively on people's activities of daily living, on their sense of physical and mental health as well as on their quality of life. Likewise many patients of the ambulatory HIV centre at the University Hospital Basel in Switzerland, report severe exhaustion and signs that indicated fatigue. In order to provide evidence-based care to these patients, a clinical practice program was developed basing on a comprehensive literature review. The program has been implemented and assists nurses to effectively assess and provide an intervention to those patients with HIV/AIDS who suffer from fatigue. The program includes the elements: screening, systematic assessment and intervention. For the systematic assessment, the Global Fatigue Index and a visual analogue scale are utilized. In this article, relevant literature has been reviewed for the development of an evidence-based program of care for patients living with HIV. Such an approach is perceived to positively affect the outcomes of patients living with HIV.