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Calcineurin inhibitors (CNIs) are essential medications for many people living with solid-organ transplants. CNI therapy helps prevent organ transplant rejection, though it requires monitoring to ensure efficacy and safety. Here we report a case of a young kidney transplant recipient who developed a severe and debilitating complication of CNI therapy that resolved following CNI dose reduction. CNI-induced pain syndrome (CIPS) may affect as many as 1 in 20 people treated with CNIs, including many of the 62 900 people in the United Kingdom who require CNI therapy following organ transplantation. Clinical presentation, severity and duration are variable, though the condition is often associated with elevated serum alkaline phosphatase levels. Limited awareness of CIPS, compounded by the potential for severe symptoms to develop even when CNI blood levels are within the standard therapeutic range, risks delayed recognition and significant patient suffering, as this case report highlights. Appropriate clinical suspicion of CIPS is thus imperative to limit patient harm and resource use associated with this under-recognised and potentially serious condition.