Background: The publication of articles in peer-reviewed scientific journals is a fairly complex and stepwise process that involves responding to referees’ comments. Little guidance is available in the biomedical literature on how to deal with such comments. Objective: The objective of this article is to provide guidance to notice writers on dealing with peer review comments in a way that maximizes the chance of subsequent acceptance. Methods: This will be a literature review and review of the author’s experience as a writer and referee. Results: Where possible, the author should consider revising and resubmitting rather than sending an article elsewhere. A structured layout for responding to referees’ comments is suggested that includes the 3 golden rules: 1) Respond completely; 2) Respond politely; and 3) Respond with evidence. Conclusion: Responding to referees’ comments requires the writer to overcome any feeling of personal attack, and to instead concentrate on addressing referees’ concerns in a courteous, objective, and evidence based way.