In the months before and years since Medicare Part D's implementation in January 2006, many have been concerned with beneficiaries' ability to benefit from the complex program. A systematic review of published Medline and gray literature from January 1, 2005, to August 20, 2009, was undertaken to evaluate Medicare beneficiaries' knowledge about Part D and how this knowledge informed decisions regarding enrollment and plan choice. Thirty articles that reported original results describing seniors' knowledge of the Part D benefit, decision to enroll, or selection of plans; results from patient surveys addressing these issues; or results that analyzed enrollment data or plan selection patterns were included. Of these 30 articles, 10 described beneficiaries' knowledge, 12 described enrollment and plan choices, and eight described knowledge and choice. Across studies and years, beneficiaries' knowledge of the Part D program and benefit structure and design was poor, particularly with regard to the coverage gap and the low-income subsidy. Beneficiaries had great difficulty choosing the lowest-cost Part D plans and were disinclined to switch plans to improve their benefits. Knowledge deficits, enrollment problems, and plan choice difficulties were most pronounced during Part D implementation in early 2006 but persisted in subsequent years of the benefit. Beneficiaries' knowledge and choices should be monitored on an ongoing basis to inform potential changes to the Part D program.