Many have raised concerns about the reproducibility of biomedical research. In this Perspective, the authors address this "reproducibility crisis" by distilling discussions around reproducibility into a simple guide to facilitate understanding of the topic.Reproducibility applies both within and across studies. The following questions address reproducibility within studies: "Within a study, if the investigator repeats the data management and analysis will she get an identical answer?" and "Within a study, if someone else starts with the same raw data, will she draw a similar conclusion?" Contrastingly, the following questions address reproducibility across studies: "If someone else tries to repeat an experiment as exactly as possible, will she draw a similar conclusion?" and "If someone else tries to perform a similar study, will she draw a similar conclusion?"Many elements of reproducibility from clinical trials can be applied to preclinical research (e.g., changing the culture of preclinical research to focus more on transparency and rigor). For investigators, steps toward improving reproducibility include specifying data analysis plans ahead of time to decrease selective reporting, more explicit data management and analysis protocols, and increasingly detailed experimental protocols, which allow others to repeat experiments. Additionally, senior investigators should take greater ownership of the details of their research (e.g., implementing active laboratory management practices, such as random audits of raw data [or at least reduced reliance on data summaries], more hands-on time overseeing experiments, and encouraging a healthy skepticism from all contributors). These actions will support a culture where rigor + transparency = reproducibility.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.