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Summary Background Persistent abdominal pain (PAP) poses substantial challenges to patients, physicians and healthcare systems. The possible aetiologies of PAP vary widely across organ systems, which leads to extensive and repetitive diagnostic testing that often fails to provide satisfactory answers. As a result, widely recognised functional disorders of the gut–brain interaction, such as irritable bowel syndrome and functional dyspepsia, are often diagnosed in patients with PAP. However, there are a number of less well‐known differential diagnoses that deserve consideration. Aim To provide a comprehensive update on causes of PAP that are relatively rare in occurrence. Methods A literature review on the diagnosis and management of some less well‐known causes of PAP. Results Specific algorithms for the diagnostic work‐up of PAP do not exist. Instead, appropriate investigations tailored to patient medical history and physical examination findings should be made on a case‐by‐case basis. After a definitive diagnosis has been reached, some causes of PAP can be effectively treated using established approaches. Other causes are more complex and may benefit from a multidisciplinary approach involving gastroenterologists, pain specialists, psychologists and physiotherapists. This list is inclusive but not exhaustive of all the rare or less well‐known diseases potentially associated with PAP. Conclusions Persistent abdominal pain (PAP) is a challenging condition to diagnose and treat. Many patients undergo repeated diagnostic testing and treatment, including surgery, without achieving symptom relief. Increasing physician awareness of the various causes of PAP, especially of rare diseases that are less well known, may improve patient outcomes.