People, domestic animals, and wildlife are all exposed to numerous environmental threats, including harmful algal blooms (HABs). However, because animals exhibit wide variations in diet, land use and biology, they are often more frequently or heavily exposed to HAB toxins than are people occupying the same habitat, making them sentinels for human exposures. Historically, we have taken advantage of unique physiological characteristics of animals, such as the sensitivity of canaries to carbon monoxide, to more quickly recognize threats and help protect human health. As HAB events become more severe and widespread worldwide, exposure and health outcome data for animals can be extremely helpful to predict, prevent, and evaluate human exposures and health outcomes. Applying a One Health approach to investigation of HABs means that lessons learned from animal sentinels can be applied to protect people, animals and our shared environment.