Thioredoxin (TRX) family proteins are involved in various biologic processes by regulating the response to oxidative stress. Nucleoredoxin (NRX), a relatively uncharacterized member of the TRX family protein, has recently been reported to regulate the Wnt/β-catenin pathway, which itself regulates cell fate and early development, in a redox-dependent manner. In this review, we describe the TRX family proteins and discuss in detail the similarities and differences between NRX and other TRX family proteins. Although NRX possesses a conserved TRX domain and a catalytic motif for oxidoreductase activity, its sequence homology to TRX is not as high as that of the close relatives of TRX. The sequence of NRX is more similar to that of tryparedoxin (TryX), a TRX family member originally identified in parasite trypanosomes. We also discuss the reported properties and potential physiologic roles of NRX.