Polymer nanoparticles (NPs) represent one of the most innovative non-invasive approaches for drug delivery applications. NPs main objective is to convey the therapeutic molecule be they drugs, proteins, or nucleic acids directly into the target organ or tissue. Many polymers are used for the synthesis of NPs and among the currently most employed materials several biocompatible synthetic polymers, namely polylactic acid (PLA), poly lactic-co-glycolic acid (PLGA), and polyethylene glycol (PEG), can be cited. These molecules are made of simple monomers which are naturally present in the body and therefore easily excreted without being toxic. The present review addresses the different approaches that are most commonly adopted to synthetize biocompatible NPs to date, as well as the experimental strategies designed to load them with therapeutic agents. In fact, drugs may be internalized in the NPs or physically dispersed therein. In this paper the various types of biodegradable polymer NPs will be discussed with emphasis on their applications in drug delivery. Close attention will be devoted to the treatment of cancer, where both active and passive targeting is used to enhance efficacy and reduce systemic toxicity, and to diseases affecting the central nervous system, inasmuch as NPs can be modified to target specific cells or cross membrane barriers.