A computer-implemented method for trusting digitally signed files in the absence of verifiable signature conditions may include (1) receiving, from an agent on at least one endpoint device, signature information that indicates that a file encountered by the endpoint device has been digitally signed, (2) generating, based at least in part on the signature information received from the endpoint device, a reputation for the file that indicates the file's trustworthiness, (3) receiving a request from an additional agent for reputation information for the file, and (4) sending, in response to receiving the request, the reputation for the file to the additional agent to enable the additional agent to determine the trustworthiness of the file in the absence of verifiable signature conditions. Various other methods, systems, and computer-readable media are also disclosed.