In this chapter, a detailed review of the current understanding of the physical processes of droplet breakup in a high-pressure homogenizer (HPH) is presented, covering breakup mechanisms by laminar shear in the gap inlet and its boundary layers, by local turbulence in the gap exit jet, and by cavitation. Experimental evidence of the effetcts of homogenization pressure, Thoma number, dispersed and continuous phase viscosity, and dispersed phase volume fraction in relation to implications on dominant mechanisms of droplet breakup is also discussed.