There are multiple opportunities to participate in team science, leading to long-term benefits (eg, research impact, novelty, productivity). Scholars are not well-trained in how to choose among these opportunities, often learning via trial and error. The ability to navigate collaborations is framed by several principles and considerations: (1) locus of control (what control we have over our own behavior) and how it affects academic job satisfaction; (2) the scarcity mindset that may manifest as a result of the fear of missing future opportunities; and (3) power dynamics and inequities (eg, among women and racial/ethnic minority individuals). To provide a more systematic approach to weighing academic opportunities, the authors offer 30 questions across six overlapping domains. The domains include: the big picture (eg, Is the opportunity a building block for your career?), context (eg, How much do you have on your plate?), person (eg, Who is asking?), team (eg, Is the team productive?), role (eg, Will you lead or assist?), and outcomes (eg, Might the opportunity lead to publications and/or grants?). We offer advice for decision-making. For example, when presented with an opportunity involving a significant time commitment, it is useful to allow at least 24 hours before deciding. The authors offer advice and sample language for communicating your decision. Although every situation is different, there are several fundamental issues and questions to consider when one is presented with a new opportunity—these questions are suggested for mentors and mentees.