Advances in understanding molecular mechanisms and targets in immune regulation have led to the widespread use of biologic targeted therapies, and, as such, reformed the course of many disabling diseases. However, with their expanded use, various side-effects, including cutaneous, have emerged. Many times a clear-cut relationship exists between the drug and the clinical manifestations; however, when a biopsy is warranted, various histopathological patterns may be observed and may cause confusion to the dermatopathologist. The aim of this review is to shed light on the different histopathological patterns observed as a manifestation secondary to biologics.