Sexual dimorphisms contribute, at least in part, to the severity and occurrence of a broad range of neurodegenerative, cardiovascular, and bone disorders. In addition to hormonal factors, increasing evidence suggests that stem cell‐intrinsic mechanisms account for sex‐specific differences in human physiology and pathology. Here, we discuss sex‐related intrinsic mechanisms in adult stem cell populations, namely mesoderm‐derived stem cells, neural stem cells (NSCs), and neural crest‐derived stem cells (NCSCs), and their implications for stem cell differentiation and regeneration. We particularly focus on sex‐specific differences in stem cell‐mediated bone regeneration, in neuronal development, and in NSC‐mediated neuroprotection. Moreover, we review our own recently published observations regarding the sex‐dependent role of NF‐κB‐p65 in neuroprotection of human NCSC‐derived neurons and sex differences in NCSC‐related disorders, so‐called neurocristopathies. These observations are in accordance with the increasing evidence pointing toward sex‐specific differences in neurocristopathies and degenerative diseases like Parkinson's disease or osteoporosis. All findings discussed here indicate that sex‐specific variability in stem cell biology may become a crucial parameter for the design of future treatment strategies.