Most people associate cystic fibrosis (CF) with lung disease. Although this is the major cause of morbidity and mortality, CF is in fact a multi-organ disease. Patients with CF are living longer. Accompanying their increased life expectancy are complications not previously encountered. One of the less obvious concerns is that of renal dysfunction associated with long-term exposure to aminoglycosides as well as renally toxic immunosuppressants in lung transplant recipients. This article reviews what is known about the extent of the problem, summarizes what the current practices of measuring and monitoring renal function in patients with CF, and makes suggestions for alternative approaches. In particular, the potential role of cystatin C will be discussed.