In 2003, 20 years ago, Tracy Wilkins and David Lyerly at the Virginia Polytechnic Institute in Blacksburg, VA, USA, published a paper in the Journal of Clinical Microbiology entitled "Clostridium difficile Testing: after 20 Years, Still Challenging” (JCM, 2003;41:531–534). Paul Simon was not talking about C. difficile when he used the words “still crazy”, he was talking about his wife! Here we are, another 20 years further on, and it feels like "Déjà vu all over again", words attributed to baseball player Yogi Berra. I cannot tell a lie – for years I thought it was Yogi Bear, the Hanna-Barbera character! But then I realised that a cartoon bear could not possibly be as erudite as Homer Simpson! C. difficile, a Gram positive, spore-forming, anaerobe, is the primary aetiological agent of pseudomembranous colitis and the leading cause of antimicrobial-associated diarrhoea. C. difficile virulence is classically attributed to two large glucosylating toxins: toxin A and toxin B, with the role of a third, binary toxin, still debated. With an estimated 4-500,000 cases annually in the USA and medical costs totalling up to US$3 billion, C. difficile infection (CDI) is a significant economic and medical burden across the globe. Epidemic strains of C. difficile have emerged in several parts of the world, notably North America but also in Australia (although they were American strains). The reasons for this are poorly understood but require some knowledge of C. difficile evolution. Diagnosis and surveillance of CDI rely on having available a sufficiently sensitive and specific laboratory test suitable for both purposes. Currently such a test does not exist, leading to much confusion about what to do. In the UK, the English Department of Health has mandated that a test to detect free toxin in faeces should be used for the laboratory diagnosis of disease. In the USA, molecular tests to detect toxin genes have been implemented widely leading to suggestions of over-reporting of CDI cases. In Australia, both approaches are being used adding to the confusion about what exactly is being counted as a case of CDI. This presentation will discuss this conundrum.