More than 50 years have passed since the first allogeneic hematopoietic stem cell transplant in patients; however, the promise of other stem cell populations for tissue replacement and repair remains unachieved. When considering cell-based interventions for personalized medicine, the factors influencing therapeutic success and safety are more complicated than for traditional small-molecule pharmacological agents and protein biologics. Failure to progress personalized stem cell therapies to the clinic has resulted from complications that include an incomplete understanding of developmental programs and the diversity of host-donor interactions. In order to more rapidly extend the use of stem cells to the clinic, a better understanding of the different stem cell sources and the implications of their host interactions is required. In this review, we introduce the currently available sources and highlight recent literature that instructs the potential and limitations of their use.