High-pressure processing (HPP) has been the most adopted nonthermal processing technology in the food industry with a current ever-growing implementation, and meat products represent about a quarter of the HPP foods. The intensive research conducted in the last decades has described the molecular impacts of HPP on microorganisms and endogenous meat components such as structural proteins, enzyme activities, myoglobin and meat color chemistry, and lipids, resulting in the characterization of the mechanisms responsible for most of the texture, color, and oxidative changes observed when meat is submitted to HPP. These molecular mechanisms with major effect on the safety and quality of muscle foods are comprehensively reviewed. The understanding of the high pressure–induced molecular impacts has permitted a directed use of the HPP technology, and nowadays, HPP is applied as a cold pasteurization method to inactive vegetative spoilage and pathogenic microorganisms in ready-to-eat cold cuts and to extend shelf life, allowing the reduction of food waste and the gain of market boundaries in a globalized economy. Yet, other applications of HPP have been explored in detail, namely, its use for meat tenderization and for structure formation in the manufacturing of processed meats, though these two practices have scarcely been taken up by industry. This review condenses the most pertinent-related knowledge that can unlock the utilization of these two mainstream transformation processes of meat and facilitate the development of healthier clean label processed meats and a rapid method for achieving sous vide tenderness. Finally, scientific and technological challenges still to be overcome are discussed in order to leverage the development of innovative applications using HPP technology for the future meat industry.