Assessment of risks to humans associated with the use of chemicals requires knowledge of the hazard (toxicity) of the chemical and level of human exposure. Hazard assessment is often based on animal bioassays and quantitative exposure estimates of dermal exposure obtained from studies monitoring workers. Because human skin is an effective barrier to many chemicals, it cannot be assumed that the deposited dose is equivalent to the systemic dose. However, an estimate of systemic dose may be derived by multiplying the deposited dose by the percentage of percutaneous uptake. This correction can have major impact on the regulatory decision, because the adjusted dose used in the risk calculation may be reduced significantly, especially at high doses, when the uptake is not linearly proportional to the exposure. It is therefore important that the dermal absorption value be accurate. As outlined in this paper, numerous factors can affect percutaneous absorption. Nevertheless, many regulatory agencies will consider the use of percutaneous absorption data derived from in vivo studies to adjust the dermally deposited dose to that delivered systemically. Numerous issues must be resolved before in vitro dermal penetration studies can be used for risk assessment.