Thrombocytopenia is associated with increased mortality rates in critically ill patients. It is especially present in cases of sepsis, but can also be caused by medications or associated with the use of foreign materials. Many physiological mechanisms (immune-mediated, consumption or destruction) are involved in the decrease of platelet count. The timing and intensity of the thrombocytopenia and the clinical context can help in the differential diagnosis. The aetiology of the thrombocytopenia must be elucidated in order to optimize the therapeutic management.