Methods and systems to implement a physical device to differentiate amongst multiple virtual machines (VM) of a computer system. The device may include a wireless network interface controller. VM differentiation may be performed with respect to configuration controls and/or data traffic. VM differentiation may be performed based on VM-specific identifiers (VM IDs). VM IDs may be identified within host application programming interface (API) headers of incoming configuration controls and data packets, and/or may be looked-up based on VM-specific MAC addresses associated with data packets. VM IDs may be inserted in API headers of outgoing controls and/or data packets to permit a host computer system to forward the controls and/or packets to appropriate VMs. VM IDs may be used look-up VM-specific configuration parameters and connection information to reconfigure the physical device on a per VM basis. VM IDs may be used look-up VM-specific security information with which to process data packets.