NAD(P)(H)-dependent oxidoreductase catalyzes the reduction of ketones or aldehydes to prepare a wide variety of valuable chiral alcohols or amines. However, expensive cofactors are absolutely required for the biocatalytic processes with oxidoreductases, which severely hinder their industrial applications. Consequently, the issue on reducing cofactor costs has become one of the major focuses in the field of biocatalysis. With the substantial development in recent years, a number of strategies have been proposed and implemented to solve the cofactor issues in the oxidoreductase catalyzed biocatalysis, including the establishment of cofactor regeneration system, the improvement of endogenous cofactor availability via metabolic engineering and the development of biomimetic agents to replace cofactors. In this review, recent trends and advances on these strategies are presented, and respective advantages and shortcomings are also discussed with a number of examples.