The "escape-and-radiate" hypothesis predicts that antipredator defenses facilitate adaptive radiations by enabling escape from constraints of predation, diversified habitat use, and subsequently speciation. Animals have evolved diverse strategies to reduce the direct costs of predation, including cryptic coloration and behavior, chemical defenses, mimicry, and advertisement of unprofitability (conspicuous warning coloration). Whereas the survival consequences of these alternative defenses for individuals are wellstudied, little attention has been given to the macroevolutionary consequences of alternative forms of defense. Here we show, using amphibians as the first, to our knowledge, large-scale empirical test in animals, that there are important macroevolutionary consequences of alternative defenses. However, the escape-andradiate hypothesis does not adequately describe them, due to its exclusive focus on speciation. We examined how rates of speciation and extinction vary across defensive traits throughout amphibians. Lineages that use chemical defenses show higher rates of speciation as predicted by escape-and-radiate but also show higher rates of extinction compared with those without chemical defense. The effect of chemical defense is a net reduction in diversification compared with lineages without chemical defense. In contrast, acquisition of conspicuous coloration (often used as warning signals or in mimicry) is associated with heightened speciation rates but unchanged extinction rates. We conclude that predictions based on the escape-and-radiate hypothesis must incorporate the effect of traits on both speciation and extinction, which is rarely considered in such studies. Our results also suggest that knowledge of defensive traits could have a bearing on the predictability of extinction, perhaps especially important in globally threatened taxa such as amphibians.escape-and-radiate | coevolution | speciation | extinction | amphibians T he idea that defensive traits determine macroevolutionary patterns was originally suggested in the plant literature (1) to explain heightened diversity. In this hypothesis, the presence of repellent chemical defenses was proposed to open up an "adaptive zone" of diverse ecological opportunities and hence promote speciation by adaptive radiation. This became known as the "escape-and-radiate" hypothesis (2). Similarly, it has been suggested that bright coloration can reduce the constraints of hiding, enabling niche expansion and promoting diversification in animal prey (3, 4). The escape-and-radiate hypothesis is influential in the adaptive radiation literature (2, 5, 6) but has been tested surprisingly rarely (6-8). The very few macroevolutionary studies on animal defenses focus only on coloration, are small-scale, and often only consider net diversification or comparisons of species richness in relation to the defensive trait of interest (5, 9, 10). For instance, one recent study on poison dart frogs included defense-based diversification analyses as part of an examination o...