Photodynamic therapy (PDT) uses a combination of molecular oxygen, light and a photosensitizer (PS) to generate singlet oxygen or reactive oxygen species (ROS), which can eradicate tumoral cells. All currently approved PSs for cancer treatment are molecular PSs. To date, no nanoparticlebased PSs are used clinically although it has widely been shown that nanotechnology may help to improve the properties of molecular PSs; for instance, molecular PSs suffer from some intrinsic limitations that undermine their therapeutic efficacy. In the present minireview, the most critical weaknesses exhibited by molecular PSs are described, and the potential use of nanoparticles (NPs) to address them and to reach the clinics is discussed.