The subject disclosure is directed towards using primary data deduplication concepts for more efficient access of data via content addressable caches. Chunks of data, such as deduplicated data chunks, are maintained in a fast access client-side cache, such as containing chunks based upon access patterns. The chunked content is content addressable via a hash or other unique identifier of that content in the system. When a chunk is needed, the client-side cache (or caches) is checked for the chunk before going to a file server for the chunk. The file server may likewise maintain content addressable (chunk) caches. Also described are cache maintenance, management and organization, including pre-populating caches with chunks, as well as using RAM and/or solid-state storage device caches.