Mixture exposure against several stressors is what organisms in the environment typically experience, and combined effects resulting from this are well documented. Risk management often still focuses on the assessment of individual priority compounds. Because of the large number of possible mixtures and their variability in time, experimental investigation of every conceivable mixture for their adverse effects is not a viable option. Instead, during the past decade, modeling approaches have been discussed in ecotoxicology that allow the prediction of expected combination effects based on the knowledge of the biological activity of the individual components. This contribution summarizes mixture exposure situations where consensus has been achieved about extrapolation techniques. In particular, for simultaneous exposure and for sequential exposure with no intervening recovery, currently available evidence demonstrates reasonable predictability of combined effects from the information of the individual mixture components. By contrast, when organisms are exposed to pulsed exposure with recovery periods or when nonchemical stressors interfere, there is still an open research field as how to account for these types of interaction.