More and more investigations confirm that nanoparticles are incapable of overcoming the intact skin barrier in vivo. Do nanoparticles still have a future in dermal drug delivery? Unlike many other topically applied substances, nanoparticles have not been reported to utilize the intercellular penetration pathway and preferentially make use of the follicular penetration pathway. Deep penetration into the follicular ducts has been described for a variety of particles and appears to be strongly influenced by particle size. For targeted drug delivery, smart nanoparticles are required which are able to release their loaded drugs subsequent to internal or external trigger stimuli, and thereby enable the translocation of the active agents into the viable epidermis. In the recent manuscript, three nanoparticles systems are summarized and compared which release their model drugs upon different trigger mechanisms. The BSA hydrogel nanoparticles release their model drug TRITC-dextran by passive diffusion due to a concentration gradient via a porous surface. The protease-triggered controlled release BSA nanoparticles release their model drug if they are applied simultaneously with protease nanoparticles, resulting in an enzymatic degradation of the particles and a release of the model drug FITC. Finally, the IR-triggered controlled release AuNP-doped BSA nanoparticles release their model drug FITC after photoactivation with wIRA. For all three nanoparticle systems, the release of their model drugs could be observed. For the first nanoparticle system, only low follicular penetration depths were found which might by due do an agglomeration effect. For the last two nanoparticle systems, deep follicular penetration and even an uptake by the sebaceous glands were verified. In conclusion, it could be demonstrated that nanoparticles do have a future in dermal drug delivery if smart nanoparticle systems are utilized which are able to release their drug at specific times and locations within the hair follicle. (C) 2016 Elsevier B.V. All rights reserved.