The field of biological cardiac pacing, which aims to improve upon, supplement and, eventually, to replace electronic pacing has come a long way since its inception more than a decade ago. Broadly, research has been focused on gene and cell therapy. In this Review, Rosen and colleagues highlight milestones achieved through the construction of a 'roadmap' in biological pacing, and discuss the barriers that remain to be overcome before clinical trials of biological pacing can be begun.