In recent years, much attention has been focused on the impact of climate change, particularly via ocean acidification (OA), on marine organisms. Studying the impact of OA on long-living organisms, such as sharks, is especially challenging. When the ocean waters absorb anthropogenic carbon dioxide (CO2), slow-growing shark species with long generation times may be subjected to stress, leading to a decrease in functionality. Our goal was to examine the behavioral and physiological responses of sharks to OA and the possible impacts on their fitness and resilience. We conducted a systematic review in line with PRISMA-Analyses, of previously reported scientific experiments. We found that most studies used CO2 partial pressures (pCO2) that reflect representative concentration pathways for the year 2100 (e.g., pH ~7.8, pCO2 ~1000 μatm). Since there is a considerable knowledge gap on the effect of OA on sharks, we utilized existing data on bony fish to synthesize the available knowledge. Given the similarities between the behaviors and physiology of these two superclasses’ to changes in CO2 and pH levels, there is merit in including the available information on bony fish as well. Several studies indicated a decrease in shark fitness in relation to increased OA and CO2 levels. However, the decrease was species-specific and influenced by the intensity of the change in atmospheric CO2 concentration and other anthropogenic and environmental factors (e.g., fishing, temperature). Most studies involved only limited exposure to future environmental conditions and were conducted on benthic shark species studied in the laboratory rather than on apex predator species. While knowledge gaps exist, and more research is required, we conclude that anthropogenic factors are likely contributing to shark species’ vulnerability worldwide. However, the impact of OA on the long-term stability of shark populations is not unequivocal.