This review summarizes properties of various naturally occurring compounds with reported calmodulin (CaM)-inhibitory properties which include about 159 natural products belonging to different structural classes. Most inhibitors are alkaloid and peptide type of compounds and have been isolated from a wide variety of natural sources, including many plant species. Among the most potent natural anti-CaM substances, however, are several animal venoms and the antibiotic polymixin. The largest number of compounds described were discovered by means of enzymatic functional assays.