Since 2002, the first edition of this best-selling book has helped thousands of newly appointed principal investigators successfully transition to running their own labs. But changes in technology continue to transform the way science is done, affecting ways in which labs communicate and collaborate, organize data and supplies, and keep current on the latest developments. The culture of science has also evolved, as more scientists explore non-academic career paths, seek new ways to communicate information and ideas, and acquire skills and knowledge outside of their field. In the second edition of this book, Kathy Barker has substantially revised the text, offering PIs advice on adapting to the changes and challenges that the years have brought. New topics include collaboration contracts, performance evaluations, communicating with non-scientists, tips for succeeding on the tenure track, and professional development. With this book as a guide, any new or aspiring PI will be well-equipped to manage personnel, time, and institutional responsibilities with confidence.