Medicare Part D went into effect on January 1, 2006. Anyone with Part A or B is eligible for Part D, which covers mostly self-administered drugs. It was made possible by the passage of the Medicare Modernization Act of 2003. To receive this benefit, a person with Medicare must enroll in a stand-alone Prescription Drug Plan (PDP) or public Part C healh plan with integrated prescription drug coverage (MA-PD). These plans are approved and regulated by the Medicare program, but are actually designed and administered by various sponsors including charities, integrated health delivery systems, unions and health insurance companies; almost all these sponsors in turn use pharmacy benefit managers in the same way as they are used by sponsors of health insurance for those not on Medicare. Unlike Original Medicare (Part A and B), Part D coverage is not standardized (though it is highly regulated by the Centers for Medicare and Medicaid Services). Plans choose which drugs they wish to cover (but must cover at least two drugs in 148 different categories and cover all or "substantially all" drugs in the following protected classes of drugs: anti-cancer; anti-psychotic; anti-convulsant, anti-depressants, immuno-suppressant, and HIV and AIDS drugs). The plans can also specify with CMS approval at what level (or tier) they wish to cover it, and are encouraged to use step therapy. Some drugs are excluded from coverage altogether and Part D plans that cover excluded drugs are not allowed to pass those costs on to Medicare, and plans are required to repay CMS if they are found to have billed Medicare in these cases.

Under the 2003 law that created Medicare Part D, the Social Security Administration offers an Extra Help program to lower-income seniors such that they have almost no drug costs; in addition approximately 25 states offer additional assistance on top of Part D. It should be noted again for beneficiaries who are dual-eligible (Medicare and Medicaid eligible) Medicaid may pay for drugs not covered by Part D of Medicare. Most of this aid to lower-income seniors was available to them through other programs before Part D was implemented.

Coverage by beneficiary spending is broken up into four phases: deductible, initial spend, gap (infamously called the "donut hole"), and catastrophic. Under a CMS template, there is usually a $100 or so deductible before benefits commence (maximum of $415 in 2019) followed by the initial spend phase where the templated co-pay is 25%, followed by gap phase (where originally the templated co-pay was 100% but that will fall to 25% in 2020 for all drugs), followed by the catastrophic phase with a templated co-pay of about 5%. The beneficiaries' OOP spend amounts vary yearly but are approximately as of 2018 $1000 in the initial spend phase and $3000 to reach the catastrophic phase. This is just a template and about half of all Part D plans differ (for example, no initial deductible, better coverage in the gap) with permission of CMS, which it typically grants as long as the sponsor provides at least the actuarial equivalent value.