Systematic description of structure-activity relationships (SARs) of data sets and structure-property relationships (SPRs) is of paramount importance in medicinal chemistry and other research fields. To this end, structure-activity similarity (SAS) maps are one of the first tools proposed to describe SARs using the concept of activity landscape modeling. One of the major goals of the SAS maps is to identify activity cliffs defined as chemical compounds with high similar structure but unexpectedly very different biological activity. Since the first publication of the SAS maps more than ten years ago, these tools have evolved and adapted over the years to analyze various types of compound collections, including structural diverse and combinatorial sets with activity for one or multiple biological end points. The development of SAS maps has led to general concepts that are applicable to other activity landscape methods such as \"consensus activity cliffs\" (activity cliffs common to a series of representations or descriptors) and \"selectivity switches\" (structural changes that completely invert the selectivity pattern of similar compounds against two biological end points). Herein, we review the development, practical applications, limitations, and perspectives of the SAS and related maps which are intuitive and powerful informatics tools to computationally analyze SPRs.