Biotoxicity of individual metals is well investigated but that of metal mixture, an environmental reality, in the developing metal mixture, is relatively obscure. Experimental evidences had shown that this mixture could give rise to combined effects that were different from the effect of metals one by one. This review provides an overview of recent research on metal mixture toxicity and the methods employed to predict their toxic combined effects. The two established reference models, the concentration-addition model and the independent-addition model, were used for evaluating the combined effect from the biological activities of the metal mixtures. While the reference models had provided reasonable tools for analyzing the combined effects, the actual predictions for binary metal mixtures showed often somewhat less than additive combined effects compared to what has been observed. As the metal bioavailability is oriented by several environmental factors as well as the toxicodynamics of metals is highly compound-specific, the non-interactive combined effects may be confused with different processes of the interactions. Thus, for improving the predictability of combined effects in metal mixture toxicity, numerous qualitative and quantitative analysis are required for the processes governing the toxicokinetics and dynamics of metals in aquatic organisms.