The present invention extends to methods, systems, and computer program products for reliable messaging using clocks with synchronized rates. In some embodiments, a message source adds at least an interaction ID and TTL value to a message. The message source begins a countdown timer having duration of the TTL value. The message source transmits the message to the destination computer system. The message source detects expiration of a retransmission interval corresponding to the message. The message source determines if the message requires acknowledgment. In other embodiments, a message destination receives a message that includes at least an interaction ID and TTL value. The message destination determines that the message is to be processed. The message destination begins a countdown timer having duration of the TTL value. The message destination processes the message and updates an interaction cache location that corresponds to the interaction ID.