Nanotechnology has been setting benchmarks for the last two decades, but the origins of this technology reach back to ancient history. Today, nanoparticles of both metallic and non-metallic origin are under research and development for applications in various fields of biology/therapeutics. Physiologically important metals are of concern because they are compatible with the human system in terms of absorption, assimilation, excretion, and side effects. There are several physiologically inorganic metals that are present in the human body with a wide range of biological activities. Some of these metals are magnesium, chromium, manganese, iron, cobalt, copper, zinc, selenium and molybdenum. These metals are synthesized in the form of nanoparticles by different physical and chemical methods. Physiologically important nanoparticles are currently under investigation for their bio-medical applications as well as for therapeutics. Along with the applicative aspects of nanoparticles, another domain that is of great concern is the risk assessment of these nanoparticles to avoid unnecessary hazards. It has been seen that these nanoparticles have been shown to possess toxicity in biological systems. Conventional physical and chemical methods of metal nanoparticle synthesis may be one possible reason for nanoparticle toxicity that can be overcome by synthesis of nanoparticles from biological sources. This review is an attempt to establish metal nanoparticles of physiological importance to be the best candidates for future nanotechnological tools and medicines, owing to the acceptability and safety in the human body. This can only be successful if these particles are synthesized with a better biocompatibility and low or no toxicity.