The recent discovery that cell-free DNA can be shed into the bloodstream as a result of tumour cell death has generated great interest. Numerous studies have demonstrated tumour-specific alterations in DNA recovered from plasma or serum of patients with various malignancies, a finding that has potential for molecular diagnosis and prognosis. The implication is that tumour-derived nucleic acids of human or viral origin can be retrieved from blood by a minimally invasive procedure, and used as a surrogate tumour marker to monitor the course of the disease or aid in early diagnosis. The present review will describe the main areas of ongoing investigation, with particular emphasis on technical issues and available data of clinical relevance.