An interface between USB devices employs isolation techniques to provide electrical isolation of a USB signal for transmission of the USB signal between the devices. Unidirectional isolator channels are utilized to transmit the USB signals, and a selection of an isolator channel operating in an intended direction is performed by either direction control logic or a USB hub function. Logic may be employed to detect a device attempting to initiate a USB signal. The logic operates to enable a transmitter on a receiving side and isolate the USB signal through an isolator channel operating in a transmission direction.