<p>The Essential Medicines List (EML) provides international guidance for the selection of effective, safe, and essential drugs. Retained drugs were identified as medicines listed in both the 1^st and 24^th EML editions. The study aims to pharmacologically assess and to distinguish established therapeutic value from questionable or obsolete current relevance. Retained drugs were assessed by therapeutic value and indication-specific justification. Listed indications and the importance developments were compared between the 1^st (1977) and 24^th EML (2025). The justification of listing was assessed by guideline recommendations, efficacy and safety, scope of clinical usage, and availability of alternatives. A structured assessment algorithm was applied to assign drugs to therapeutic value categories. 129 retained drugs were assessed. Most EML indications did not change (<i>n</i> = 65), followed by specifications (<i>n</i> = 26), additions (<i>n</i> = 24), narrowing (<i>n</i> = 8), or change (<i>n</i> = 6). 71 drugs (55.0%) were classified as having constant importance, 20 (15.5%) as increasing, and 38 (29.5%) as declining. Drugs can be categorized in preserved and clearly justified value, niche value, requiring indication correction, and obsolescence. Nineteen drugs were identified where continued EML listing warrants discussion, mainly due to restricted or second-choice use, reduced efficacy, high pathogen resistance, and toxicity issues. Historical retention on the EML does not necessarily indicate unchanged therapeutic value. A structured pharmacological assessment can distinguish valuable from obsolete retained drugs. EML-listed drugs require regular reassessment to ensure that future EML editions remain clinically justified and relevant for public health.</p>