Since their initial description in 1857, gold nanoparticles have been used extensively in the fields of diagnostics and therapeutics. Now, gold nanoparticles are engineered to target the delivery of potent anti-cancer therapeutics to solid tumors to improve either their safety or efficacy or both. Described in this chapter is the development of one such nanotherapeutic, termed CYT-6091, that targets the delivery of tumor necrosis factor alpha (TNF) to solid tumors. Outlined in the presentation is a discussion of nanoparticles and specifically colloidal gold, an historical review on the biology of TNF and its limited use in the clinic when administered systemically, and finally, how gold nanoparticles bound with TNF may improve the safety and efficacy profiles of TNF.