Invasive plants and fire create substantial challenges for land managers in the deserts of North America. Invasive plants can compete with native plants, alter wildlife habitat, and promote the spread of fire where it was historically infrequent. Increased fire frequency in the Mojave and Sonoran deserts has converted native shrublands to alien annual grasslands. Fire suppression and overgrazing of livestock has allowed native woody shrubs, such as mesquite (Prosopis spp.) and creosotebush (Larrea tridentata), to invade perennial grasslands in the Chihuahuan Desert, and native trees, such as juniper (Juniperus spp.) and pinyon (Pinus spp.), to invade sagebrush (Artemisia spp.) steppe in the Great Basin. The reintroduction of fire can be complicated by the positive effect of fire on alien invasive plants, and the subsequent effects of invasives on post-fire establishment by native species. Invasive alien grasses especially benefit from fire, and promote recurrent fire, in many cases to the point where native species cannot persist and native plant assemblages are converted to alien-invaded annual grasslands. This vegetation type-conversion can affect wildlife ranging from herbivores to carnivores and reduce overall biodiversity. The effective management of many wildlife species can depend on the control of invasive plants and the maintenance of appropriate fire regimes. Fire can be used to either control invasive species or to restore historical fire regimes. However, the decision to use fire as a management tool must consider the potential interrelationships between fire and invasive species. Historical fire regimes did not occur in the presence of many invasive plants that are currently widespread, and the use of fire may not be a feasible or appropriate management action if fire-tolerant invasive plants are present. The management of fire and invasive plants must be closely integrated for each to be managed effectively.