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The use of anticholinesterases to reverse residual neuromuscular block at the end of surgery became routine practice in the 1950s. These drugs could only be used when recovery from block was established [two twitches of the train-of-four (TOF) count detectable] and concern was expressed about their cholinergic side-effects. By the 1990s, it was recognized that failure to reverse residual block adequately to a TOF ratio (TOFR) >0.7 was associated with increased risk of postoperative pulmonary complications (POPCs) following the long-acting non-depolarizing neuromuscular blocking drug (NDNMBD) pancuronium. By 2003, and the introduction of acceleromyography, a TOFR ≥0.9 was considered necessary to protect the airway from aspiration before tracheal extubation. It was also considered that four, not two, twitches of the TOF should be detectable before neostigmine was given. Use of any NDNMBD was subsequently shown to be associated with increased risk of POPCs, but it was thought that neostigmine reduced that risk. Recently, there has been conflicting evidence that use of neostigmine might increase the incidence of POPCs. Although sugammadex has been shown to rapidly reverse profound neuromuscular block from aminosteroidal agents, there is currently no evidence that sugammadex is superior to neostigmine in its effect on POPCs. Other new antagonists, including cysteine to degrade CW002 and calabadion 1 and 2 to antagonize aminosteroidal and benzylisoquinolium NDNMBDs, are being studied in preclinical and clinical trials. Quantitative neuromuscular monitoring is essential whenever a NDNMBD is used to ensure full recovery from neuromuscular block.