Studying the mechanism of interaction of metals with enzymes of the heme biosynthetic pathway has revealed a great deal of understanding of the regulation of the pathway and a possible insight into the toxicology of certain metals. Both positive and negative effects of metals on heme biosynthesis and catabolism can be demonstrated. The understanding of these interactions has given us a clearer picture of certain of the descriptive events known to occur in toxic states induced by these metals. Unfortunately, the studies have also driven us to appreciate the even more complex nature of the biosynthetic and metabolic pathways for heme than was originally hypothesized. It can be predicted that the next 5 years should lead to many more revelations and potential treatment modalities for toxic states induced by metals or genetic diseases where heme biosynthesis does not occur normally.