Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited due to systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These pressurized, reservoir-based iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. In the mouse models, device delivery of cytotoxic agents resulted in enhanced drug accumulation in the tumor and tumor shrinkage. In dogs, device delivery resulted in large local drug concentrations and low systemic drug exposure. These devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors.