Numerous metals have found their application in diagnostics as imaging agents, in therapeutics, etc. and twenty‐first century research has focused its trend on developing nanoparticulate form of metals. These metallic nanoparticles (MNPs) are easy to synthesize and sizes as low as 5 nm can be achieved. The high‐surface area‐to‐volume ratio and varied surface functionalization allow for its application in drug delivery and targeted therapies. The geometry and properties of MNP is quite different and unique, unlike the properties of their bulk form. Such properties often influence its uptake, distribution, elimination, and toxicity. The benefits of MNPs are associated with toxicities as well, with bare metallic nanoparticles reported for their toxicities in in vitro and in vivo models. MNPs generally prove to be toxic due to various reasons like reactive oxygen species (ROS) generation, inducement of oxidative stress, disturbing the integrity of the cytoskeleton, damaging DNA, and inducing rogue cell signaling. These toxicity issues have not convinced regulatory bodies and pose significant hurdles in translating to clinical settings. Attempts have been made to surface modify MNPs with polymers like polyethylene glycol to reduce their opsonization, increase biocompatibility, and reduce toxicity. This chapter provides an insight into the accumulation of MNPs and factors influencing the toxicity of MNP. The research on toxicity and pharmacokinetics of metals along with its application needs ample focus. The toxicity of MNPs needs to be addressed and further extensive research is essential on pharmacokinetics and toxicity studies for successful application and uses in the healthcare sector.