The Ten Simple Rules (TSR) series covers topics ranging from the very broad (career paths, scientific communication) to the more specific (illustrating figures, managing software), and all the various TSRs focus on one’s scientific and professional development. The present TSR shares that goal, and is authored by consumers and suppliers of research opportunities. Here, the consumers are individuals in their late teenage years, i.e., late-high school (LHS) or early-college (EC), who are either considering or actively searching for their first opportunity in a research lab at a university, national lab or beyond (ANM and JC). The suppliers are university researchers (CM and PEB), along with the views of a seasoned educator (MC). We write this TSR for three reasons. First, research requests have become more frequent in recent years and, while our general area has been computational biology, that’s probably secondary: the Rules articulated here may apply equally well across many disciplines. Second, in the past decade or so there has been an astonishing increase in the intensity of HS students, on many fronts—in terms of technical skill-sets (e.g., mastery of programming languages), academic preparation and scientific sophistication (e.g., courses in advanced math), and beyond (e.g., career-related ambitions, such as searching for research opportunities!). Finally, some of these HS students who spent time in our laboratories have gone on to productive and rewarding research careers, underscoring that this is a formative stage in one’s scientific career. Reflecting on these experiences, through the eyes of trainee and mentor, we hope that this TSR affords some useful tips on whether research is right for you, how to go about procuring a research position, and the broader topic of navigating the LHS/EC stage of your own scientific trajectory.