A recirculating aquaculture system (RAS) represents a form of aquaculture with a present and future vision. However, the rapid industrialization of the technology has shown that there are still opportunities for improvement, considering that the RAS operational process chain should be based on fish biology. The concept is that fish should be considered a technical subcomponent in a RAS, determining an adapted and functional process technology. Fish farmed in RAS seem to be considered organisms with great plasticity, but ultimately they are small biological machines that, in concrete terms, remain a black box in biological and physiological terms. Thus, the biological responses of fish in RAS should provide all the knowledge necessary to apply them in a technical environment, and not the other way around. Fish are generally overloaded with stressors that have a negative impact on production in RAS. What do fish farmed in RAS in Chile tell us? That physiological interactions are complex and multifaceted and could result in productivity losses in the early post-seeding stages at sea. How do we apply this in the field? Through biomarkers that reflect the biological capacities of fish in an integrated, quantitative, and predictive manner. The PhysioRAS strategy improves understanding of the interactions between osmoregulatory capacity, immune response, acid-base balance, sexual maturity, among others. This knowledge is essential for obtaining robust smolts that guarantee the best productive performance for the rest of the production cycle at sea. The information necessary to understand these concepts is presented and discussed in this paper based on current scientific knowledge and field results in Chile.