Systemic drugs are increasingly being administered intranasally. We highlight the potential problems and the effect of nasal pathology on absorption and bioavailability. There is insufficient information to evaluate the effect of these factors on therapeutic effectiveness. However, there is evidence that nasal pathology can influence mucociliary clearance and absorption, so the prescriber should recognise and consider the effect of any intranasal pathology. We suggest that, until the effects of these factors are quantified, patients who are about to embark on long-term intranasal medication should have a rhinological assessment, particularly if they have any nasal symptoms. By doing this, factors that may cause reduced bioavailability can be identified. It would also prevent pre-existing mucosal changes being wrongly attributed to nasal drugs.