The pixels of remote images often contain more than one distinct material (mixed pixels), and so their spectra are characterized by a mixture of spectral signals. Since 1971, a shared effort has enabled the development of techniques for retrieving information from mixed pixels. The most analyzed, implemented, and employed procedure is spectral unmixing. Among the extensive literature on the spectral unmixing, nineteen reviews were identified, and each highlighted the many shortcomings of spatial validation. Although an overview of the approaches used to spatially validate could be very helpful in overcoming its shortcomings, a review of them was never provided. Therefore, this systematic review provides an updated overview of the approaches used, analyzing the papers that were published in 2022, 2021, and 2020, and a dated overview, analyzing the papers that were published not only in 2011and 2010, but also in 1996 and 1995. The key criterion is that the results of the spectral unmixing were spatially validated. The Web of Science and Scopus databases were searched, using all the names that were assigned to spectral unmixing as keywords. A total of 454 eligible papers were included in this systematic review. Their analysis revealed that six key issues in spatial validation were considered and differently addressed: the number of validated endmembers; sample sizes and sampling designs of the reference data; sources of the reference data; the creation of reference fractional abundance maps; the validation of the reference data with other reference data; the minimization and evaluation of the errors in co-localization and spatial resampling. Since addressing these key issues enabled the authors to overcome some of the shortcomings of spatial validation, it is recommended that all these key issues be addressed together. However, few authors addressed all the key issues together, and many authors did not specify the spatial validation approach used or did not adequately explain the methods employed.