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Protein microarray or protein chip is an important tool in proteomics. However, duplicating the success of the DNA chip for the protein chip has been difficult. This account discusses a key issue in protein microarray development, i.e., surface chemistry. Ideally, the surface chemistry for protein microarray fabrication should satisfy the following criteria: the surface resists nonspecific adsorption; functional groups for the facile immobilization of protein molecules of interest are readily available; bonding between a protein molecule and a solid surface is balanced to provide sufficient stability but minimal disturbance on the delicate three-dimensional structure of the protein; linking chemistry allows the control of protein orientation; the local chemical environment favors the immobilized protein molecules to retain their native conformation; and finally, the specificity of linking chemistry is so high that no pre-purification of proteins is required. Strategies to achieve such an ideal situation are discussed, with successful examples from our laboratories illustrated. Finally, the need of surface technology for membrane protein microarray fabrication is addressed.