The principal objective of regional chemotherapy is tumor cell kill. The rationale for regional delivery is based on the steep dose/response curve exhibited by most antineoplastic agents. Intraarterial (IA) chemotherapy has the potential advantage of increased drug concentration at the tumor site, decreased systemic drug levels, and continuous tumor cell exposure to an antineoplastic agent. Despite these advantages, the use of IA chemotherapy has not been universally accepted. This is in part due to the difficulties associated with establishing and maintaining arterial access. Considerable improvement in the techniques and efficacy of regional therapy for head and neck cancer will be necessary before there is widespread clinical acceptance. These improvements must be based on anatomic and pharmacologic factors that ensure success of regional therapy. In addition, the development of safe, reliable delivery systems will be necessary. Part 1 of this two-part article will review these factors and discuss delivery systems.