The purpose of this article is to review and discuss the factors affecting high pressure processing (HPP) in juices and beverages. The inactivation of microorganisms by HPP depends on numerous factors, including the magnitude of the pressure and the holding time, process temperature, compression and decompression rates, the microbiota, and the intrinsic properties of juices and beverages. Although extensive HPP research has been performed to characterize many of these factors, a number of issues, such as the rates of compression and decompression, still remain unresolved and need further investigation. In addition, some published results are conflicting and do not provide enough evidence to develop juice HPP “safe-harbor” parameters to achieve a minimum 5-log reduction of the pertinent microorganism and produce safe fruit juices and beverages. HIGHLIGHTS