Self-discovering transaction accelerators improve communications between a client and a server. A client directs a message to a server. A client-side transaction accelerator intercepts the message, terminates the connection with the client, and accelerates the request by replacing segments of data with references. The accelerated request is forwarded to a server-side transaction accelerator through a new connection. The server-side transaction accelerator reconstructs the message by replacing the reference with segment data in a persistent segment store accessible to the server-side transaction accelerator. The reconstructed request is then provided to the server. Accelerations may occur in any direction of communication. Persistent segment stores can be pre-populated with segment data from other transaction accelerators and anticipated transactions. The persistent segment store can store segments that are data segmented based on content of the data and can be independent of transaction protocol, application, and device.