Nanomaterials, with their diverse dimensions, shapes and surface functional groups, may interact with biomolecules in various ways. In this paper, we reviewed recent advances on the research of the effect of nanomaterials on biomolecular reactions and the use of nano-bio-complexes in biosensors. Much evidence has clearly indicated that nanomaterials are excellent matrixes for the immobilization of enzymes and such complexes often exhibits even higher activities than native enzymes. Consequently, a large amount of highly sensitive biosensors have been developed based on such nano-bio-complexes. We also stressed the importance of nanomaterials on the reactions of nucleic acids. By exploiting the interactions between AuNPs and DNA, several groups have developed a series of novel biosensors for the detection of DNA target and other biologically important molecules. While the state-of-the-art researches are mainly focused on the study of one nanomaterial and one biomolecule, there has been evidence that integration of nano-bio-complexes might lead to much more interesting findings. For example, nanomaterials have been found to exert great impact on complicated systems such as PCR. One might expect that the realization of highly cooperated nano-bio-machines that comprise of different nanomaterials and different biomolecules would lead to highly promising diagnostic tools both in-vivo and in-vitro.