Intermittent rivers and ephemeral streams (IRES) are common worldwide and play important roles in freshwater biodiversity and biogeochemical processes. Anthropogenic threats to IRES can be broadly classified into hydrological, physical, chemical, and biological alterations that can occur specifically during dry (e.g., sediment mining) or wet phases (e.g., water withdrawals). These alterations often increase vulnerability of IRES to biotic invasions and have cascading effects in adjacent and downstream habitats. Climate change could directly affect flow, temperature regimes, and surface-groundwater interactions in IRES and indirectly affect their nutrient deposition and transport. Climate change, human population growth, and anticipated increased demand for water mean more perennial rivers will become intermittent, and IRES may cease flow and dry more often, potentially exacerbating anthropogenic impacts. Increased awareness of the currently underappreciated ecological values of IRES may encourage development of better management tools and biomonitoring methods to evaluate and potentially mitigate these impacts.