One of the hardest things is insuring the individuals being released have their survival instincts. Survival techniques are usually based from parent to offspring. They have the genetics of the species, but not the natural memetics.
Difficult to pick one particular aspect. As the successful learning of survival techniques has already been touched upon in another answer, I’ll point out the genetic differences. Captive populations often suffer from decreased genetic diversity and increased risk of inbreeding. Modern captive breeding efforts do their best to alleviate this, but the fact of the matter is that captive populations are usually small and therefore not very diverse. This lack of genetic diversity can mean that the species doesn’t have the genetic variability to survive in a dynamic natural environment.
Another, simpler problem is finding a habitat to reintroduce the species into. Oftentimes their original homes will have been changed by human activity, and may no longer be able to support the species. This has happened in the vast majority of the gray wolf’s former range in North America.
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