We report the results of a survey of laws and regulations governing the sale and possession of needles and syringes in the United States and its territories and discuss legal and public health proposals to increase the availability of sterile syringes, as a human immunodeficiency virus (HIV) transmission prevention measure, for persons who continue to inject drugs. Every state, the District of Columbia (DC), and the Virgin Islands (VI) have enacted state or local laws or regulations that restrict the sale, distribution, or possession of syringes. Drug paraphernalia laws prohibiting the sale, distribution, and/or possession of syringes known to be used to introduce illicit drugs into the body exist in 47 states, DC, and VI. Syringe prescription laws prohibiting the sale, distribution, and possession of syringes without a valid medical prescription exist in 8 states and VI. Pharmacy regulations or practice guidelines restrict access to syringes in 23 states. We discuss the following legal and public health approaches to improve the availability of sterile syringes to prevent bloodborne disease among injection drug users: (1) clarify the legitimate medical purpose of sterile syringes for the prevention of HIV and other blood-borne infections; (2) modify drug paraphernalia laws to exclude syringes; (3) repeal syringe prescription laws; (4) repeal pharmacy regulations and practice guidelines restricting the sale of sterile syringes; (5) promote professional training of pharmacists, other health professionals, and law enforcement officers about the prevention of blood-borne infections; (6) permit local discretion in establishing syringe exchange programs; and (7) design community programs for safe syringe disposal.