Cardenolides are toxic to animals through inhibition of the enzyme Na+/K+-ATPase, which is responsible for maintaining the sodium and potassium ion gradients across the cell membranes.

[1] The term derives from card- "heart" (from Greek καρδία kardiā) and the suffix -enolide, referring to the lactone ring at C17.

[3] Species such as the monarch, queen, and plain tiger ingest the cardenolides contained in the milkweeds (Asclepias) that they mostly feed on and sequester as larvae for defense as adults.

In addition to milkweeds and other members of the Apocynaceae, plants in at least 12 botanical families have convergently evolved cardenolides, used as a chemical defense mechanism against herbivores.

These cardenolide-resistant insect species convergently evolved this resistance through similar amino-acid substitutions in the alpha subunit of the enzyme Na+/K+-ATPase.