Skin represents an effective barrier against the penetration of external agents into the human body. Nevertheless, recent research has shown that small particles, especially in the nanosized range, can not only penetrate through the skin but also work as vectors to transport active molecules such as contrast agents or drugs. This knowledge has opened new perspectives on nanomedicine and controlled drug delivery. On the other hand, micro- and nanoplastics represent a form of emerging pollutants, and their concentration in the environment has been reported to drastically increase in the last years. The possible penetration of these particles through the skin has become a major concern for human health. If the actual primary toxicity of these materials is still debated, their possible role in the transport of toxic molecules through the skin, originating as secondary toxicity, is surely alarming. In this review paper, we analyze and critically discuss the most recent scientific publications to underline how these two processes, (i) the controlled delivery of bioactive molecules by micro- and nano-structures and (ii) the unwanted and uncontrolled penetration of toxic species through the skin mediated by micro- and nanoparticles, are deeply related and their efficiency is strongly affected by the nature, size, and shape of the particles.