Through the use of various layer-by-layer polyelectrolyte (PE) coating schemes, such as the common poly(diallyldimethylammonium chloride)-poly(4-styrenesulfonic acid) (PDADMAC-PSS) system, the mammalian cellular uptake of gold nanorods can be tuned from very high to very low by manipulating the surface charge and functional groups of the PEs. The toxicity of these nanorods is also examined. Since the PE coatings are individually toxic, the toxicity of nanorods coated in these PEs is measured and cells are found to be greater than 90% viable in nearly all cases, even at very high concentrations. This viability assay may not be a complete indicator of toxicity, and thus gene-expression analysis is used to examine the molecular changes of cells exposed to PDADMAC-coated nanorods, which enter cells at the highest concentrations. Indicators of cell stress, such as heat-shock proteins, are not significantly up- or down-regulated following nanorod uptake, which suggests that PDADMAC-coated gold nanorods have negligible impact on cell function. Furthermore, a very low number of genes experience any significant change in expression (0.35% of genes examined). These results indicate that gold nanorods are well suited for therapeutic applications, such as thermal cancer therapy, due to their tunable cell uptake and low toxicity.