The Mississippi River flows 3,734 km from its source at Lake Itasca, Minnesota to its outlet at the Gulf of Mexico. Along its course, it collects water from portions of two Canadian provinces and 41 % of the conterminous United States. Although greatly altered for navigation and flood control throughout much of its length, the Mississippi River remains an important fishery resource that provides habitat for 188 species of fishes and recreational and commercial fishing opportunities. The objectives of this chapter are to describe the contemporary fisheries habitat throughout the Mississippi River, identify how management to achieve human benefits influences the fishes and their habitats, and summarize efforts to conserve and enhance fish habitat. The 826-km headwater reach is entirely in Minnesota and remains largely unaltered. The reaches that extend 1,059 km from St. Anthony Falls, Minnesota to above the confluence with the Missouri River near St. Louis, Missouri have been altered by impoundment that has affected floodplain function, increased sedimentation of backwaters, and homogenized the formerly diverse aquatic habitats. After the confluence with the Missouri River, the Mississippi River flows freely for 1,849 km to the Gulf of Mexico. The alterations of the free-flowing reaches of greatest significance to the fisheries resource are reducing the duration and height of the flood pulse as a consequence of shortening the river channel, disconnection of the river from its historic and present floodplain, and loss of secondary channel-island complexes. Engineering features to improve commercial navigation have also added habitat and, when wisely manipulated, can be used to rehabilitate habitat. Some aspects of water quality have improved, but legacy chemicals and nutrient-laden inflows and sediments remain problems. Although true restoration in the sense of restoring all environmental conditions to an unaltered state is unlikely, the future value of the Mississippi River as a fisheries resource will depend on actively maintaining diverse and accessible aquatic habitats to support food webs and water quality suitable for fishes.