Provided are a method, system, and program for processing Input/Output (I/O) requests to a storage space having a plurality of storage devices. An Input/Output (I/O) request is received directed to a target location in a target storage device in the storage space, wherein the storage space includes at least two adaptors providing access to the storage devices. A determination is made of a plurality of paths to the target storage device, wherein a path comprises one adaptor or one adaptor and at least one intervening storage device. A determination is made of a characteristic of each determined path. One path is selected based on the determined characteristic and the I/O request is transmitted to the adaptor in the selected path.