Nurses play an important role in the care of patients treated with radiotherapy (RT) for skin conditions such as skin cancers. A series of four articles will aim to supplement general oncology nurse training by providing a scientific basis to better understand the skin and its diseases, the use of RT in skin, and the management of necessary acute skin RT reactions to achieve best patient outcomes. The first article focused on the role of the nurse within the radiation oncology department and the initial patient assessment. This second article describes the anatomy, physiology, pathology and radiobiology of skin and its diseases. These concepts are fundamental to the understanding of how acute effects develop during treatment and how to best care for them. The transition time of normal keratinocytes in the epidermis from creation to demise (10-14 days) is discussed as essential to understanding the timing of acute RT effects. The effect of RT on DNA, and the different effects of RT on normal cells versus tumour cells, which underscore fractionation and normal tissue conservation, are also discussed. Finally, this article addresses the late effects of RT in normal skin, accelerated repopulation, types of skin cancers and their relative radiosensitivities, and the effects of RT on benign skin diseases. The third article will describe the skin RT prescription and plan, especially in relation to volume and dose; and the fourth will show how the nurse, by applying the knowledge from the previous articles, can predict, explain and care for the acute side effects that may arise during a course of skin radiotherapy.