ZnO nanostructured materials, such as films and nanoparticles, could provide a suitable platform for development of high performance biosensors due to their unique fundamental material properties. This paper reviews different preparation techniques of ZnO nanocrystals and material issues like wettability, biocompatibility and toxicity, which have an important relevance to biosensor functionality. Efforts are made to summarize and analyze existing results regarding surface modification and molecular attachments for successful biofunctionalization and understanding of the mechanisms involved. A section is devoted to implementations of tailored surfaces in biosensors. We end with conclusions on the feasibility of using ZnO nanocrystals for biosensing.