The ability of certain foods to impair or augment the absorption of various vitamins and minerals has been recognized for many years. However, the contribution of botanical dietary supplements (BDSs) to altered micronutrient disposition has received little attention. Almost half of the US population uses some type of dietary supplement on a regular basis, with vitamin and mineral supplements constituting the majority of these products. BDS usage has also risen considerably over the last 2 decades, and a number of clinically relevant herb-drug interactions have been identified during this time. BDSs are formulated as concentrated plant extracts containing a plethora of unique phytochemicals not commonly found in the normal diet. Many of these uncommon phytochemicals can modulate various xenobiotic enzymes and transporters present in both the intestine and liver. Therefore, it is likely that the mechanisms underlying many herb-drug interactions can also affect micronutrient absorption, distribution, metabolism, and excretion. To date, very few prospective studies have attempted to characterize the prevalence and clinical relevance of herb-micronutrient interactions. Current research indicates that certain BDSs can reduce iron, folate, and ascorbate absorption, and others contribute to heavy metal intoxication. Researchers in the field of nutrition may not appreciate many of the idiosyncrasies of BDSs regarding product quality and dosage form performance. Failure to account for these eccentricities can adversely affect the outcome and interpretation of any prospective herb-micronutrient interaction study. This review highlights several clinically relevant herb-micronutrient interactions and describes several common pitfalls that often beset clinical research with BDSs.