Surface-active agents (surfactants) form the foundation of an effective detergent formulation. As such, surfactants are a major component of laundry detergents. Depending on multiple factors, the amount of residual detergent surfactants in clothing after washing varies but may be sufficient to elicit skin irritation in susceptible individuals and in patients with existing dermatologic disorders. The goal of this review is to examine the relationship between surfactants commonly used in laundry detergent formulations and their potential for skin irritancy. In this context, the role of surfactants in achieving broad-spectrum cleaning performance in laundry is discussed, and currently available methodologies to evaluate and measure the effect of surfactant exposure on the skin are reviewed.