Surface acoustic wave (SAW) devices are considered to be very promising in providing a high-performance sensing platform with wireless and remote operational capabilities. In this review, the basic principles of SAW devices and Love-mode SAW-based biosensors are discussed first to illustrate the need for surface enhancement for the active area of a SAW sensor. Then some of the recent efforts made to incorporate nanostructures into SAW sensors are summarized. After that, a computational approach to elucidate the underlying mechanism for the operations of a Love-mode SAW biosensor with nanostructured active surface is discussed. Finally, a modeling example for a Love-mode SAW sensor with skyscraper nanopillars added to in its active surface along with some selected results is presented.