Plants, like all other organisms, have evolved different mechanisms to maintain physiological concentrations of essential metal ions and to minimize exposure to non-essential heavy metals. Some mechanisms are ubiquitous because they are also required for general metal homeostasis, and they minimize the damage caused by high concentrations of heavy metals in plants by detoxification, thereby conferring tolerance to heavy metal stress. Other mechanisms target individual metal ions (indeed some plants have more than one mechanism to prevent the accumulation of specific metals) and these processes may involve the exclusion of particular metals from the intracellular environment or the sequestration of toxic ions within compartments to isolate them from sensitive cellular components. As a first line of defense, many plants exposed to toxic concentrations of metal ions attempt to prevent or reduce uptake into root cells by restricting metal ions to the apoplast, binding them to the cell wall or to cellular exudates, or by inhibiting long distance transport. If this fails, metals already in the cell are addressed using a range of storage and detoxification strategies, including metal transport, chelation, trafficking, and sequestration into the vacuole. When these options are exhausted, plants activate oxidative stress defense mechanisms and the synthesis of stress-related proteins and signaling molecules, such as heat shock proteins, hormones, and reactive oxygen species.