Functionalized nanoparticles are heralded as part of the future with regards to targeted cell and nuclear delivery. However, direct intracellular and intranuclear delivery has, until recently, been difficult to achieve owing to the impermeable nature of the plasma and nuclear membranes. During the past 15 years, a range of peptides, termed cell-penetrating peptides (CPPs), which have the ability to translocate into living cells, have been discovered. Thus, in more recent years, the combination of CPPs with nanoparticles, enabling CPP-mediated cell delivery, has opened up many avenues of research. This review discusses the use of various CPPs, focusing on tat peptide, to functionalize nanoparticles and the possible move from the laboratory to the clinic.