Isolation and study of metal tolerant and hypersensitive strains of higher plant (and yeast) species has greatly increased our knowledge of the individual pathways that are involved in tolerance. Plants have both constitutive (present in most phenotypes) and adaptive (present only in tolerant phenotypes) mechanisms for coping with elevated metal concentrations. Where studies on the mechanisms of tolerance fall down is in their failure to integrate tolerance mechanisms within cell or whole-plant function by not relating adaptive mechanisms to constitutive mechanisms. This failure often distorts the relative importance of a proposed tolerance mechanism, and indeed has confused the search for adaptive mechanisms. The fundamental goal of both constitutive and adaptive mechanisms is to limit the perturbation of cell homeostasis after exposure to metals so that normal or near-normal physiological function may take place. Consideration of the response to metals at a cellular rather than a biochemical level will lead to a greater understanding of mechanisms to withstand elevated levels of metals in both contaminated and uncontaminated environments. Recent advances in the study of Al, As, Cd, and Cu tolerance and hypersensitivity are reported with respect to the cellular response to toxic metals. The role of genetics in unravelling tolerance mechanisms is also considered.