Lake Michigan, a 58,000-km(2) freshwater inland sea, is large enough to have persistent basin-scale circulation yet small enough to enable development of approximately balanced budgets for water, energy, and elements including carbon and silicon. Introduction of nonindigenous species-whether through invasion, intentional stocking, or accidental transplantation-has transformed the lake's ecosystem function and habitat structure. Of the 79 nonindigenous species known to have established reproductive populations in the lake, only a few have brought considerable ecological pressure to bear. Four of these were chosen for this review to exemplify top-down (sea lamprey, Petromyzon marinus), middle-out (alewife, Alosa pseudoharengus), and bottom-up (the dreissenid zebra and quagga mussels, Dreissena polymorpha and Dreissena rostriformis bugensis, respectively) transformations of Lake Michigan ecology, habitability, and ultimately physical environment. Lampreys attacked and extirpated indigenous lake trout, the top predator. Alewives outcompeted native planktivorous fish and curtailed invertebrate populations. Dreissenid mussels-especially quagga mussels, which have had a much greater impact than the preceding zebra mussels-moved ecosystem metabolism basin-wide from water column to bottom dominance and engineered structures throughout the lake. Each of these non indigenous species exerted devastating effects on commercial and sport fisheries through ecosystem structure modification.