The excellent tolerability of therapeutic doses of paracetamol (acetaminophen) is a major factor in the very wide use of the drug. The major problem in the use of paracetamol is its hepatotoxicity after an overdose. Hepatotoxicity has also been reported after therapeutic doses, but critical analysis indicates that most patients with alleged toxicity from therapeutic doses have taken overdoses. Importantly, prospective studies indicate that therapeutic doses of paracetamol are an unlikely cause of hepatotoxicity in patients who ingest moderate to large amounts of alcohol. Controlled clinical trials have found that paracetamol is very well tolerated by the gastrointestinal tract. While variable results have been found in case control studies, most studies have shown no change or a small increase in the relative risk of perforations, ulcer or bleeding in the upper gastrointestinal tract. However, associations between the use of paracetamol and gastrointestinal toxicity, as well as with chronic renal disease and asthma, are very likely to reflect biases in some case control studies. In particular, such biases may be caused by the perceived high tolerability of paracetamol in these diseases. The consequent use of paracetamol in these diseases states then leads to an apparent association between paracetamol and the disease. Despite metabolism of paracetamol to reactive compounds, hypersensitivity reactions are rare, although urticaria occurs in occasional patients. Paracetamol appears to be well tolerated during pregnancy although prospective studies are required.