Human aldo-keto reductase family 1 member C3 (AKR1C3) is known as a hormone activity regulator and prostaglandin F (PGF) synthase that regulates the occupancy of hormone receptors and cell proliferation. Because of the overexpression in metabolic diseases and various hormone-dependent and -independent carcinomas, as well as the emergence of clinical drug resistance, an increasing number of studies have investigated AKR1C3 inhibitors. Here, we briefly review the physiological and pathological function of AKR1C3 and then summarize the recent development of selective AKR1C3 inhibitors. We propose our viewpoints on the current problems associated with AKR1C3 inhibitors with the aim of providing a reference for future drug discovery and potential therapeutic perspectives on novel, potent, selective AKR1C3 inhibitors.