Submissions are subject to an article processing charge and, according to the journal, papers are not to be excluded on the basis of lack of perceived importance or adherence to a scientific field.

In September 2009, as part of its article-level metrics program, PLOS One made its full online usage data, including HTML page views and PDF or XML download statistics, publicly available for every published article.

[25] PLOS One is built on several conceptually different ideas compared to traditional peer-reviewed scientific publishing in that it does not use the perceived importance of a paper as a criterion for acceptance or rejection.

The idea is that, instead, PLOS One only verifies whether experiments and data analysis were conducted rigorously, and leaves it to the scientific community to ascertain importance, post publication, through debate and comment.

This pre-publication peer review will concentrate on technical rather than subjective concerns and may involve discussion with other members of the Editorial Board and/or the solicitation of formal reports from independent referees.

If published, papers will be made available for community-based open peer review involving online annotation, discussion, and rating.

In an effort to facilitate publication of research on topics outside, or between, traditional science categories, it does not restrict itself to a specific scientific area.

The rejection letter concerned Ingleby and Head's paper about differences in PhD-to-postdoc transition between male and female scientists.

[41] On March 3, 2016, the editors of PLOS One initiated a reevaluation of an article about the functioning of the human hand[42] due to outrage among the journal's readership over a reference to "Creator" inside the paper.

[45] A less sympathetic explanation for the use of "Creator" was suggested to The Chronicle of Higher Education by Chinese-language experts who noted that the academic editor listed on the paper, Renzhi Han, previously worked at the Chinese Evangelical Church in Iowa City.

[46] Sarah Kaplan of The Washington Post presented a detailed analysis of the problem, which she named #CreatorGate, and concluded that the journal's hasty retraction may have been an even bigger offense than the publication of the paper in the first place.

On August 27, 2018, the editors of PLOS One initiated a reevaluation of an article they published two weeks earlier submitted by Brown University School of Public Health assistant professor Lisa Littman.

PLOS One psychology academic editor Angelo Brandelli Costa acted as a reviewer criticizing the methods and conclusion of the study in a formal comment, saying, "The level of evidence produced by the Dr. Littman's study cannot generate a new diagnostic criterion relative to the time of presentation of the demands of medical and social gender affirmation.

However, we have also determined that the study, including its goals, methodology, and conclusions, were not adequately framed in the published version, and that these needed to be corrected.

In her correction, Littman emphasized that the article was "a study of parental observations which serves to develop hypotheses", saying "Rapid-onset gender dysphoria (ROGD) is not a formal mental health diagnosis at this time.

Additional research that includes AYAs, along with consensus among experts in the field, will be needed to determine if what is described here as rapid-onset gender dysphoria (ROGD) will become a formal diagnosis.