Despite the significance of patients' adherence to prescription drug treatments, it is estimated that > 30% of the drugs that are prescribed to older persons are not self-administered in accordance with the instructions. This research examines which factors affect the adherence to prescription drugs of older Israelis and tests whether the Theory of Planned Behavior (TPB) can explain their adherence. In this cross-sectional survey design, a reliable and valid structured questionnaire, based on the TPB, was administered to a convenience sample of 207 independent older persons who were taking prescription drugs. One-fifth of the sample reported that they did not adhere to their medication regime. The older persons' self-reported adherence to treatment was related to the quantity of drugs that they were required to take and to whether or not they received the support of a primary caregiver. The more confidence that the older persons had in their physician's level of professionalism, the greater their self-reported adherence to the prescription drugs. Behavioral beliefs, behavioral attitudes, perceived behavioral control, and subjective norms were related to the older persons' intention to self-administer medication. We conclude that nurses have an important responsibility in assessing the medication-taking behaviors of older adults.