The aim of this review is to combine the knowledge of studies on effects of nutrients on pyrrolizidine alkaloids (PAs) in Senecio with those studies of effects of PAs on herbivores and pathogens in order to predict the effects that nutrients may have on herbivores and pathogens via changes in PAs. We discuss whether these predictions match with the outcome of studies where the effect of nutrients on herbivores and insects were measured. PA concentrations in S. jacobaea, S. vulgaris and S. aquaticus were mostly reduced by NPK fertilization, with genotype-specific effects occurring. Plant organs varied in their response to increased fertilization; PA concentrations in flowers remained constant, while shoot and roots were mostly negatively affected. Biomass change is probably largely responsible for the change in concentrations. Nutrients affect both the variety and the levels of PAs in the plant. The reduced PA concentrations after NPK fertilization was expected to benefit herbivores, but no or negative responses from insect herbivores were observed. Apparently other changes in the plant after fertilization are overriding the effect of PAs. Pathogens do seem to benefit from the lower PA concentrations after fertilization; they were more detrimental to fertilized plants than to unfertilized control plants. Future studies should include the effect of each element of nutrients separately and in combinations in order to gain more insight in the effect of specific nutrients on PA content in Senecio plants.