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Hemophilia treatment relies upon replacement of the deficient factor to restore physiological levels in plasma. The development of inhibitors is the main complication of replacement therapy, which renders replacement therapy ineffective and requires the use of alternative hemostatic drugs known as bypassing agents. The hemostatic response to bypassing agents is different from patient to patient and even in the same patient during different bleeding episodes. Up to now, no routine laboratory test has been found suitable to monitor efficacy and safety of these drugs. The unpredictable clinical response to bypassing therapy and the lack of a monitoring laboratory tool renders surgery in inhibitor patients a big challenge for the risk of both bleeding and thromboembolic complications. The thrombin generation assay (TGA) has been proposed as a monitoring tool in this patient population on the basis of the results obtained both in vitro and ex vivo. This review aims to summarize the current published evidence on the use of TGA as a laboratory monitoring tool in patients with hemophilia complicated by inhibitors.