The field of nanotechnology has grown over the last two decades and made the transition from the benchtop to applied technologies. Nanoscale-sized particles, or nanoparticles, have emerged as promising tools with broad applications in drug delivery, diagnostics, cosmetics and several other biological and non-biological areas. These advances lead to questions about nanoparticle safety. Despite considerable efforts to understand the toxicity and safety of these nanoparticles, many of these questions are not yet fully answered. Nevertheless, these efforts have identified several approaches to minimize and prevent nanoparticle toxicity to promote safer nanotechnology. This review summarizes our current knowledge on nanoparticles, their toxic effects, their interactions with mammalian cells and finally current approaches to minimizing their toxicity.