Nicotinamide N-methyltransferase (NNMT) plays an important role in diverse biological processes by regulating methylation potential and the degradation of nicotinamide. Meanwhile, the aberrant expression of NNMT has been implicated in multiple cancers, metabolic and liver diseases. Therefore, there has been an emerging interest in assessing NNMT as a potential therapeutic target and discovering NNMT inhibitors over the past 5 years. Herein, we focus on the recognition, mechanism, and inhibitors of NNMT with emphasis on key advancements in the field. We also discuss future directions for the development of NNMT inhibitors.