This chapter deals with the factors that are most important in determining the level of risk that accrues from direct physical contact between the sex worker and the client. Venues for sex work range from outdoor settings such as the street and truck stops to massage parlors, brothels, private apartments, and hotels. The historical portrayal of commercial sex workers as reservoirs of infection, particularly HIV, is well documented. The most important factors affecting the risk of sexually transmitted infections (STI) are considered in the subsections: use of condoms; injected drug use (IDU); narcotics; mental health. This chapter demonstrates interrelatedness of these factors in the lives of female sex workers and the ways in which their impact is modified by the physical setting, the level of control and autonomy workers have over their conditions of work, and the degree to which they are victimized by the authorities.