Continuous long-term single-cell observation provides insight into the molecular control of cell fate. This is particularly important for rare and heterogeneous populations of cells, such as mammalian stem cells. The current lack of usable off-the-shelf hardware and software for such experiments makes their implementation technically challenging. Here I discuss the need for continuous single-cell quantification to understand molecular cell fate control as well as organizational and technical solutions for long-term imaging and tracking of stem cells.