Theories, data and knowledge continue to accumulate and become refined across many scientific fields - but what do we know about science itself? In this Review, Santo Fortunato et al. highlight efforts to understand the "science of science," insights from which could be used to optimize the pursuit of knowledge and better society. Often, scientists may appear to be productive by adhering to research within their domain, publishing many studies within their specialized area; yet here the authors note that a focused agenda may limit a researcher's ability to sense and seize opportunities for developing new ideas that are required to grow the field's knowledge. For the bold who explore new avenues of research, the benefits can be great though: analyses of publications and patents consistently reveal that rare combinations in scientific discoveries and inventions tend to garner higher citation rates. Funding could be reallocated to better reflect the burden of disease and to proactively sponsor risky projects, the authors suggest. Of note, funding schemes that are tolerant of early failure, and which reward long-term success, are more likely to generate high-impact publications than grants subject to short review cycles. As well, the authors highlight ways in which collaboration can be beneficial, noting that teams are 38% more likely than solo authors to bring novelty into familiar knowledge domains. Some other "science of science" themes Fortunato et al. touch on include: size of teams, career dynamics of scientists, coauthor credits, and more.