Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The World Health Organization (WHO) estimates that 84 million people will die of cancer between 2005 and 2015. The main weakness of most chemotherapeutic approaches to cancer treatment is that most of them are nonspecific. The polymeric nanoparticles can enhance the permeability and retention of anticancer drug and diminish the drug exposure to healthy tissues by limiting drug distribution to the target cancer. The properties of nanoparticles as precursor of a good nanomedicine are nanoparticle size, size distribution, surface morphology, surface chemistry, surface charge, surface adhesion, surface erosion, inner porosity, drug diffusivity, encapsulation efficiency, drug stability, drug release kinetics, hemodynamic and a high loading capacity to decrease the number of the carrier required for administration. Poly (lactic-co-glycolic acid) (PLGA) is one of the most effectively used biodegradable polymers for the development of nanomedicines due to its controlled and sustained release properties, low toxicity, and biocompatibility with tissue and cells. PLGA is approved by the US FDA and European Medicine Agency (EMA) in different drug delivery systems in humans. PLGA nanoparticles are commonly used for the encapsulation of various cancer related drugs and their successful delivery in vivo. The various anticancer drugs that have been investigated in PLGA nanoparticle preparations are discussed in this chapter. The application of PLGA nanoparticles has provided a promising future for the anticancer nanomedicine with high efficacy and few side effects.