Migratory species are the most important commercial fishes in the Amazon. They are also now the most threatened directly by some combination of overfishing, floodplain deforestation, and dam construction. Limited governmental monitoring and implemented regulations impede adequate management of the fisheries at adequate scale. We summarize the current stock status of the three most heavily exploited long-distance migratory species, which are two goliath catfishes (Brachyplatystoma rousseauxii and B. vaillantii) and the characiform Colossoma macropomum. In addition, we analyze impacts beyond overfishing on these species. Our results indicate: (i) the overfishing trends for these important species are either ominous or indicate the verge of collapse of the commercial fisheries based on them, and (ii) a dangerous synergy between overfishing, hydroelectric dams, and floodplain deforestation further challenge fisheries management of migratory species in the Amazon. We propose eight direct governmental actions as a proactive approach that addresses the main impacts on the fisheries. We consider that the most practical way to assess and manage overfishing of migratory species in the short run in an area as large as the main commercial fishing area in the Amazon is at market sites where enforced regulations can control fish catch. The management of the three species considered here has implications beyond just their sustainability. Their management would represent a paradigm shift where the governments assume their legal responsibilities in fishery management. These responsibilities include regulation enforcement, data collecting, inter-jurisdictional cooperation to protect migratory species at realistic life history scales, mitigation of the Madeira dams to assure goliath catfish passage to the largest western headwater region, and recognition of monitoring and managing wetland deforestation for the protection of fish and other aquatic and terrestrial biodiversity.