<p>Targeted therapies in oncology have become a mainstay in therapy of numerous types of cancers. They work by targeting and utilizing (activating, inhibiting, or modulating) molecular pathways that are crucial in pathogenesis of certain cancers and can be divided into numerous classes according to their mechanism. However, since the antigens and molecules they target can take part in homeostasis of the skin and the integument, cutaneous toxicities are a common occurrence. The frequency of certain cutaneous adverse events (CAEs) depends on the causal drug and varies even between drugs of the same class and mechanism. Rashes, pruritus, and xerosis are among the most frequent CAEs. If severe, they can negatively impact the course of treatment by causing dose reductions and even treatment cessation. Additionally, patients with cancer often exhibit a further loss in quality of life due to the CAEs. When managed accordingly and promptly, skin, hair, and nail-related adverse events can be minimized in order to avoid treatment modifications and improve patients’ quality of life. The vast majority of summarized data and management guidelines regarding this topic focus on immune checkpoint inhibitors, with a much smaller amount dedicated to other targeted therapies. This narrative review presents the current state of knowledge about the mechanisms of cutaneous toxicities during treatment with targeted oncological drugs and identifies gaps in research.</p>