Peripheral nerve blocks provide excellent pain relief and enhance the patients’ recovery from trauma and surgeries. However, the application of peripheral nerve blocks, in patients at risk for acute compartment syndrome (ACS), has long been debated due to concern for delaying or masking the diagnosis of ACS. Nevertheless, there is still no clear evidence that the properly administered and monitored peripheral nerve blocks contribute to the delayed diagnosis of ACS. Rather, breakthrough pain in patients with a functioning continuous low-concentration peripheral nerve block can be a warning sign and facilitate early recognition of ACS. We describe a scenario of a patient, whom the breakthrough postoperative pain despite wellfunctioning continuous nerve block triggered the early management of suspected ACS. We also review relevant aspects of ACS pathophysiology and peripheral nerve blocks, as well as the discussion of the previous similar case reports. Finally, the suggested concept of management of peripheral nerve block in patients at risk for ACS is presented.