Parenteral nutrition (PN) line sepsis is a common and yet poorly managed complication in hospitalised patients receiving PN. Making a clinical diagnosis is difficult as the clinical picture can be very non-specific and definitions of what constitutes line infection can vary. Once there is clinical suspicion, proving it with microbiological techniques is not an exact science. Traditional techniques have required the removal of the PN line to allow microbiologists to perform analysis of it for infection. This has obvious drawbacks as it is often not easy to replace the line in these patients and the line is often later proven not to be the source of the sepsis. Although the gold-standard technique still requires removal of the line, there has been development in the field of diagnosis line infection while conserving the line. These include intra-luminal brushings of the line, differential blood cultures and simple swabs of the line hub. These techniques are not as sensitive but reduce the problems caused by removing and re-inserting the line in these patients. The definition of PN line sepsis varies between institutions. Rates can be expressed as a true number of cases, or can be expressed correctly as a number of cases per 1000 line days to standardise rates between units of differing sizes. Rates can also be altered if the diagnostic criteria are too strict or too lax. Accurate diagnosis of PN line sepsis remains difficult in modern medical practice.