Some demonstrative embodiments include devices, systems and methods of differentiating between an Internet Protocol (IP) Multimedia Subsystem (IMS) connection and a non-IMS connection. For example, a UE may include a communication module configured to receive from an application a request to establish a Packet Data Network (PDN) connection, and to assign an IMS tag to a traffic flow identifier of the PDN connection, wherein the IMS tag indicates that the PDN connection is an IMS connection or a non-IMS connection. The communication module may be configured to receive from the application a request to handle data packets having the traffic flow identifier, and to process the request to handle the data packets based on the IMS tag assigned to the traffic flow identifier.