Variability in flow as a result of seasonal precipitation patterns is a defining element of streams and rivers in Mediterranean-climate regions of the world and strongly influences the biota of these unique systems. Mediterranean-climate areas include the Mediterranean Basin and parts of Australia, California, Chile, and South Africa. Mediterranean streams and rivers can experience wet winters and consequent floods to severe droughts, when intermittency in otherwise perennial systems can occur. Inter-annual variation in precipitation can include multi-year droughts or consecutive wet years. Spatial variation in patterns of precipitation (rain vs. snow) combined with topographic variability lead to spatial variability in hydrologic patterns that influence populations and communities. Mediterranean streams and rivers are global biodiversity hotspots and are particularly vulnerable to human impacts. Biomonitoring, conservation efforts, and management responses to climate change require approaches that account for spatial and temporal variability (including both intra- and inter-annual). The importance of long-term data sets for understanding and managing these systems highlights the need for sustained and coordinated research efforts in Mediterranean-climate streams and rivers.