You finished your PhD, have been a postdoc for a while, and you start wondering, “What's next?” Suppose you come to the conclusion that you want to stay in academia, and move up the ladder to become a principal investigator (PI). How does one reach this goal given that academia is one of the most competitive environments out there? And suppose you do manage to snatch your dream position, how do you make sure you hit the ground running? Here we report on the workshop “P2P - From Postdoc To Principal Investigator” that we organized at ISMB 2012 in Long Beach, California. The workshop addressed some of the challenges that many postdocs and newly appointed PIs are facing. Three experienced PIs, Florian Markowetz (Group Leader, Cambridge Research Institute, Cancer Research UK), Gary Bader (Associate Professor, The Donnelly Centre, University of Toronto), and Philip Bourne (Professor, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego), provided insight into the transition from a trainee to PI and shared advice on how to make the best out it.