Regulatory legislation by governments is essential for facilitating the recovery of endangered or threatened species. Protecting commercially exploited species, in particular, requires painstaking cooperation among vested parties. However, rules protecting one species may be detrimental to others. If an exploited species is only protected in a portion of its range, exploitative efforts may divert to unprotected portions or similarly valuable species. As a result, the good intentions of protecting species in a limited fashion may manifest a species-loss domino-effect. We illustrate a species-loss domino-effect using a current example from the Mississippi River basin of the United States, where roe fisheries (for caviar) have cascaded because of strict regulations and collapses of sturgeon stocks in Europe and Asia. In the Mississippi River basin the limited protection of a commercially important sturgeon species may increase exploitation in unprotected river reaches and threaten other economically important fishes. Although a species-loss domino-effect is delineated herein using an example from a freshwater fishery in the central United States, the concept should be considered and applied to terrestrial and marine species worldwide.