While being the best separation technique, chromatography also excels in sensitivity: traces in concentrations at or below the parts-per-billion (1:109) level can be detected. However, at such low levels, positive identification is difficult since a large number of compounds may emerge from the column within a short retention time range. The solution of this problem is to use substance-selective detection, i.e., detectors which respond only to certain types of compounds. In this way, two goals are simultaneously achieved: information on the chemical nature of certain compounds present in the sample can be obtained and, at the same time, interferences of co-emerging compounds of dissimilar chemical nature can be eliminated. Although selective detection is not new in chromatography— after all the colored bands observed by Tswett already represented compound characterization—its real evolution started in the early 1960s. The paper surveys the most frequently used selective detectors and discusses a few selected questions related to their application.