Normal stem cells and cancer stem cells (CSCs) share similar properties, in that both have the capacity to self-renew and differentiate into multiple cell types. In both the normal stem cell and cancer stem cell fields, there has been a great need for a universal marker that can effectively identify and isolate these rare populations of cells in order to characterize them and use this information for research and therapeutic purposes. Currently, it would appear that certain isoenzymes of the aldehyde dehydrogenase (ALDH) superfamily may be able to fulfill this role as a marker for both normal and cancer stem cells. ALDH has been identified as an important enzyme in the protection of normal hematopoietic stem cells, and is now also widely used as a marker to identify and isolate various types of normal stem cells and CSCs. In addition, emerging evidence suggests that ALDH1 is not only a marker for stem cells, but may also play important functional roles related to self-protection, differentiation, and expansion. This comprehensive review discusses the role that ALDH plays in normal stem cells and CSCs, with focus on ALDH1 and ALDH3A1. Discrepancies in the functional themes between cell types and future perspectives for therapeutic applications will also be discussed.