Aquatic environments experiencing low-oxygen conditions have been described as hypoxic, suboxic, or anoxic zones; oxygen minimum zones; and, in the popular media, the misnomer "dead zones." This review aims to elucidate important aspects underlying oxygen depletion in diverse coastal systems and provides a synthesis of general relationships between hypoxia and its controlling factors. After presenting a generic overview of the first-order processes, we review system-specific characteristics for selected estuaries where adjacent human settlements contribute to high nutrient loads, river-dominated shelves that receive large inputs of fresh water and anthropogenic nutrients, and upwelling regions where a supply of nutrient-rich, low-oxygen waters generates oxygen minimum zones without direct anthropogenic influence. We propose a nondimensional number that relates the hypoxia timescale and water residence time to guide the cross-system comparison. Our analysis reveals the basic principles underlying hypoxia generation in coastal systems and provides a framework for discussing future changes.