This talk summarizes our recent work on the coupling of surface enzymatic reactions and surface bioaffinity interactions on biopolymer microarrays to greatly improve the sensitivity and selectivity of multiplexed biosensor measurements. The surface sensitive technique of surface plasmon resonance imaging (SPRI) is used to detect the surface enzymatic transformations in real time. Three specific examples of novel coupled surface bioaffinity/surface enzymatic processes are demonstrated: (i) a surface enzymatic amplification method utilizing the enzyme Ribonuclease H (RNase H) in conjunction with RNA microarrays that permits the ultrasensitive direct detection of genomic DNA at a concentration of 1 fM without labeling or PCR amplification, (ii) the use of RNA-DNA ligation chemistry to create renewable RNA microarrays from single stranded DNA microarrays, and (iii) the use of Taq ligase and DNA coated nanoparticles for ultrasensitive SNP detection and analysis.