The infection and lysis of plankton by viruses and subsequent release of organic material couples to ocean biogeochemical cycling. However, quantifying the in situ rates of virus-induced lysis of plankton remains challenging. The modified dilution method is one of the most commonly utilised empirical approaches to estimate virus-induced killing of plankton, just as the dilution method remains central to estimates of zooplankton-induced grazing of plankton. Here, we utilise numerical simulations and theory to test the limits to robustness and accuracy of the dilution method and the modified dilution method. We find current methods are likely to overestimate the impact of zooplankton and viruses, respectively, on plankton in environments where these ecological forces are not the dominant mortality driver. We discuss how such overestimates impact our understanding of ecological pressures on plankton communities. In closing, we propose how modifications to the protocols of the (modified) dilution method may reduce the bias inherent to mortality rate estimates across a wide range of environmental conditions.