The testing of chemicals for skin irritation after an acute exposure is considered to be among the simplest of toxicology endpoints to evaluate. Historically, this process simply involved putting the chemicals of interest on the skin of a rabbit, according to the procedures described by Draize and Woodard, and observing the result. However, animal welfare concerns and uncertainty of the relevance of extrapolating rabbit test data to the human experience have brought the relevance of the rabbit test into question. With the introduction and validation of a variety of non-animal methods to identify and classify skin irritants and non-irritants, the study design process has become slightly more complex. But by considering what the project goals are, the following guidance can make the process very manageable and the resulting data extremely useful.