The Northern Humboldt Current System (NHCS) is one of the most productive seas due to its coastal upwelling producing a high abundance of zooplankton that supports the large biomass of the Peruvian anchoveta (Engraulis ringens) and other species of ecological importance such as jumbo squid (Dosidicus gigas), squat lobster (Pleuroncodes monodon), and mesopelagic fish. The predator-prey relationships in the NHCS off Peru have been studied for almost a century - but limited to a handful of species - with new discoveries in the last decades. Here we review the literature on the diet of species within the NHCS off Peru that predate on anchoveta, jumbo squid, squat lobster and mesopelagic fish (i.e. Vinciguerria lucetia and myctophids), aiming to better understand the potential impacts on threatened, protected or data deficient species, to highlight the need for inclusion of these predators in ecological models, and to inform further actions to improve the implementation of ecosystem-based fishery management (EBFM). We also comment on the impact that the environment (e.g. ENSO) has on these interactions. Our results indicate that 39 species predate on anchoveta (teleost and cartilaginous fish, marine mammals, seabirds, cephalopods, marine reptiles, and jellyfish), 10 on jumbo squid (marine mammals, teleost and cartilaginous fish), 12 on squat lobster (teleost and cartilaginous fish, cephalopods, marine mammals, and seabirds), and 9 on mesopelagic fish (cephalopods, teleost fish and marine mammals). The conservation status according to IUCN Red List of these predators is: 12 species are categorized as Threatened, 8 are Near Threatened, 17 are Least Concern, and 4 are Data Deficient. Of these, elasmobranch species were the most threatened of all taxa. Nineteen species are nationally protected (marine mammals, seabirds, marine reptiles). Ecological models have evolved in complexity, both in methods (e.g. mass balance models) and variables included (e.g. ENSO conditions); also, the number of functional groups has increased from 16 to 45. Recent diet studies should be incorporated in future trophodynamic models to increase their accuracy. ENSO is considered to be one of the major sources of variation in the NHCS impacting predator-prey interactions (e.g. prey availability, trophic plasticity) which are further discussed in this review. The results of this study can be used to improve the EBFM applied in the Peruvian anchoveta and jumbo squid fishery.