Biosensors based on localized surface plasmon resonance (LSPR) have evolved rapidly during the past decade, and LSPR sensors have been applied in environmental monitoring and clinical bioanalytical services. Different from conventional planar surface plasmon resonance (SPR) sensors, LSPR technique takes advantages of state-of- the-art nano materials and eliminates the need of complex optical components, with low cost, high accuracy, and easy for minimization. In practice, particularly in clinical applications, LSPR is still in its laboratory development phase due to the high sample complexity and low platform specificity. However, with the improvement of surface chemistry and receptor sensitivity, the specificity of LSPR is enhanced accordingly, making the technique more user friendly (reliable real-time measurement). This paper focuses on the differences between LSPR and conventional SPR, as well as the current clinical and biomedical applications with LSPR.