Replication is the cornerstone of a cumulative science. However, new tools and technologies, massive amounts of data, interdisciplinary approaches, and the complexity of the questions being asked are complicating replication efforts, as are increased pressures on scientists to advance their research. As full replication of studies on independently collected data is often not feasible, there has recently been a call for reproducible research as an attainable minimum standard for assessing the value of scientific claims. This requires that papers in experimental science describe the results and provide a sufficiently clear protocol to allow successful repetition and extension of analyses based on original data. The importance of replication and reproducibility has recently been exemplified through studies showing that scientific papers commonly leave out experimental details essential for reproduction, studies showing difficulties with replicating published experimental results, an increase in retracted papers, and through a high number of failing clinical trials. This has led to discussions on how individual researchers, institutions, funding bodies, and journals can establish routines that increase transparency and reproducibility. In order to foster such aspects, it has been suggested that the scientific community needs to develop a ‘‘culture of reproducibility’’ for computational science, and to require it for published claims. We want to emphasize that reproducibility is not only a moral responsibility with respect to the scientific field, but that a lack of reproducibility can also be a burden for you as an individual researcher. As an example, a good practice of reproducibility is necessary in order to allow previously developed methodology to be effectively applied on new data, or to allow reuse of code and results for new projects. In other words, good habits of reproducibility may actually turn out to be a time-saver in the longer run. We further note that reproducibility is just as much about the habits that ensure reproducible research as the technologies that can make these processes efficient and realistic. Each of the following ten rules captures a specific aspect of reproducibility, and discusses what is needed in terms of information handling and tracking of procedures. If you are taking a bare-bones approach to bioinformatics analysis, i.e., running various custom scripts from the command line, you will probably need to handle each rule explicitly. If you are instead performing your analyses through an integrated framework (such as Gene- Pattern, Galaxy, LONI pipeline, or Taverna), the system may already provide full or partial support for most of the rules. What is needed on your part is then merely the knowledge of how to exploit these existing possibilities. In a pragmatic setting, with publication pressure and deadlines, one may face the need to make a trade-off between the ideals of reproducibility and the need to get the research out while it is still relevant. This trade-off becomes more important when considering that a large part of the analyses being tried out never end up yielding any results. However, frequently one will, with the wisdom of hindsight, contemplate the missed opportunity to ensure reproducibility, as it may already be too late to take the necessary notes from memory (or at least much more difficult than to do it while underway). We believe that the rewards of reproducibility will compensate for the risk of having spent valuable time developing an annotated catalog of analyses that turned out as blind alleys. As a minimal requirement, you should at least be able to reproduce the results yourself. This would satisfy the most basic requirements of sound research, allowing any substantial future questioning of the research to be met with a precise explanation. Although it may sound like a very weak requirement, even this level of reproducibility will often require a certain level of care in order to be met. There will for a given analysis be an exponential number of possible combinations of software versions, parameter values, preprocessing steps, and so on, meaning that a failure to take notes may make exact reproduction essentially impossible. With this basic level of reproducibility in place, there is much more that can be wished for. An obvious extension is to go from a level where you can reproduce results in case of a critical situation to a level where you can practically and routinely reuse your previous work and increase your productivity. A second extension is to ensure that peers have a practical possibility of reproducing your results, which can lead to increased trust in, interest for, and citations of your work. We here present ten simple rules for reproducibility of computational research. These rules can be at your disposal for whenever you want to make your research more accessible – be it for peers or for your future self. Ten Simple Rules for Reproducible Computational Research