The captive breeding and reintroduction of globally threatened species are among the most difficult of all applied ecology problems. A number of lessons learned emerged from the captive breeding and reintroduction of the Kihansi Spray Toad of which several are specific to amphibians. These include the challenge of reintroducing a captive-bred amphibian species to a location where chytridiomycosis is present, as well as the potential additive and interactive effects of chytridiomycosis with other important drivers of amphibian declines including habitat loss and fragmentation and toxic compounds. A series other lessons learned emerged that have broad applicability across multiple taxa. These include the importance of (1) a long-term commitment; (2) broad base stakeholder support; (3) enhancing national capacity in biodiverse-rich lesser developed nations; (4) a collaborative, experimentally driven adaptive management approach; (5) a targeted monitoring program; (6) external evaluation; and (7) the inclusion of an exit strategy. Recent meta-analyses of translocation success of captive-bred animals also provide important insights into the design of captive breeding—reintroduction programs for threatened species.