Aroma persistence plays a key factor driving consumers’ experience during food and beverage consumption. Traditionally, aroma persistence has been studied using sensory approaches. The development of real-time mass spectrometry techniques, such as proton transfer reaction-mass spectrometry (PTR-MS) and atmospheric pressure chemical ionization-mass spectrometry (APCI-MS), has allowed us a better understanding on this complex phenomenon, highlighting the important effects of the physicochemical properties of aroma compounds on persistence. At present, the structure of aroma compounds (chemical group) has been revealed to play an important role in aroma persistence, acting in concert with human physiological factors, such as the metabolism of aroma compounds by saliva or oral cells, or the retention of aroma compounds by the salivary mucosal pellicle. Future work should be directed towards a better understanding of the effects of food matrix composition on aroma persistence, combined with the elucidation of inter-individual differences on this phenomenon. This chapter reviews the works on aroma persistence that have employed real-time mass spectrometry measurements.