Skin-derived precursors (SKPs) are an adult stem cell source with self-renewal and multipotent differentiation. Although rodent SKPs have been discussed in detail in substantial studies, human SKPs (hSKPs) are rarely reported. Understanding the biological properties and possible mechanisms underlying hSKPs has important implications for regenerative medicine particularly clinical applications, as human-derived sources are more suitable for clinical transplantation. The finding that hSKPs derivatives, such as neural and mesodermal progeny, have both in vitro and in vivo function without any genetical modification makes hSKPs a trustable, secure, and accessible resource for cell-based therapy. Here, we provide an overview of hSKPs, describing their characteristics, originations and niches, and potential applications. A comparison between traditional and innovative culture methods used for hSKPs is also introduced. Furthermore, we discuss the challenges and the future perspectives towards the field of hSKPs. With this review, we hope to point out the current stage of hSKPs and highlight the problems that remain in this field.