Hair testing for drugs of abuse is a developing technology that offers the possibility of longer detection times than is commonly obtained with urine or blood analysis. There are many uncertainties concerning how drugs enter hair and factors that affect drug deposition and residence in hair. Possible routes of drug entry include diffusion from blood, sweat, sebum, and skin and entry from the environment. Evidence is reviewed regarding the importance of each of these routes as possible contributors to drug deposition in hair. Binding to specific sites in hair may involve both electrostatic forces and weaker attractions, such as van der Waals forces. Melanin and protein constituents of hair may serve as binding sites. Recent in vitro studies suggest that the color of hair or melanin content may be the major determinant of cocaine binding and, consequently, may result in color or ethnic bias in hair testing.