Psychrotrophic bacteria are responsible for the highest spoilage of unprocessed or heated milk during storage because of their capacity to synthesize thermostable extracellular proteases and lipases leading to gelation, off-odours/flavours, loss of sensory quality and shelf life. This chapter critically describes and discusses various topics related to the sources of psychrotrophic bacteria contamination of milk as well as their spoilage potential in dairy products. In particular, the role of thermostable proteases, lipases and phospholipases on milk deterioration is deeply reviewed besides the mechanisms of regulation of those extracellular enzymes. The latest knowledge about the molecular tools effective in characterizing psychrotrophic bacteria are presented and, finally, the effective control of processing conditions for control of psychrotrophic bacteria and related enzymes are described.