Metals and minerals that depend on renal clearance may accumulate to toxic levels in patients with marginal kidney function. Toxicities of aluminum-based phosphate binders became apparent ∼25 years ago. Nephrologists now recognize cardiovascular calcification may follow use of calcium-based phosphate binders. Five lessons can be learned: (1)safety must not be assumed in absence of data; (2) all evidence for causal linkage of toxicities from therapeutics must be considered, including animal data; (3) clinical trials are unlikely to reveal the spectrum of problems from long-term drug exposure; (4) complications can remain unrecognized until late in post-introduction surveillance; (5) minerals important for normal function can be toxic with excess accumulation. Introduction of new agents necessitates caution – it is difficult to change practice once a therapeutic is commonplace. Lessons learned about hazards of past phosphate binders must be applied judiciously when evaluating long-term risks/safety of novel metal-based binders such as lanthanum carbonate.