Reliability of thin metal films and multilayers with layer thickness ranging from micrometers to nanometers is becoming more and more important not only due to the rapid development of micro/nano technology, but also because of the demands for the fundamental research interests in small scale materials. In this paper, we will introduce the state-of-the-art progress in evaluation of fatigue reliability of metal films and multilayers, mainly emphasizing size effects and the relationship between fatigue properties and microscopic structures of the materials. Our recent investigations of fatigue reliability of nanoscale Cu films and Cu-X multilayers on a polyimide substrate will be presented. Microscopic characterization of fatigue crack initiation and growth in the multilayers shows that there exists a significant variation of fatigue damage behavior with decreasing individual layer thickness of the multilayers. Furthermore, fatigue behavior and strength of the present metal films and multilayers are compared with the thin metal films investigated previously.