Although regenerative endodontic procedures have yielded an impressive body of favorable outcomes, the treatment of necrotic immature permanent teeth in particular remains to be a challenge. Recent advances in dental stem cell (DSC) research have gained increasing insight in their regenerative potential and prospective use in the formation of viable dental tissues. Numerous studies have already reported successful dental pulp regeneration following application of dental pulp stem cells, stem cells from the apical papilla, or dental follicle precursor cells in different in vivo models. Next to responsive cells, dental tissue engineering also requires the support of an appropriate scaffold material, ranging from naturally occurring polymers to treated dentin matrix components. However, the routine use and banking of DSCs still holds some major challenges, such as culture-associated differences, patient-related variability, and the effects of culture medium additives. Only in-depth evaluation of these problems and the implementation of standardized models and protocols will effectively lead to better alternatives for patients who no longer benefit from current treatment protocols.