This chapter examines the issues to address in the cover letter and the process of submitting a manuscript to a journal for peer review. It helps readers to adhere to the ethical practices of publishing scientific and medical research, write a cover letter to accompany a manuscript submission, and submit a manuscript to a journal for peer review. The cover letter is the opportunity that authors have to demonstrate both their professionalism and their adherence to publication and research ethics. Journal editors and publishers expect that everyone involved in scientific research and publication adhere to the established ethical practices of scientific communication. Many journals use an online submission-management system, which is a content-management system designed to accept manuscripts electronically and facilitate the peer-review process. The journal editor conducts an initial review of a manuscript to ensure that the manuscript is appropriate for the journal and that the authors adhered to the journal style.