Summary: The therapeutic landscape of chronic obstructive pulmonary disease (COPD) is evolving as a result of a deeper understanding of inflammatory endotypes and the recognition of persistent disease activity despite optimized inhaled therapy. The GOLD 2026 report reinforces the principles of precision medicine and identifies patients who continue to exacerbate on maximal inhaled treatment as potential candidates for biologic interventions. In this context, blood eosinophil count has emerged as a pragmatic tool to support patient selection, although it is not considered a sufficient standalone predictor of response. This article reviews the scientific rationale for targeted therapy and summarizes evidence from contemporary registration programs. The phase III trials BOREAS and NOTUS demonstrated that inhibition of IL-4/IL-13 signaling with dupilumab, added to background triple therapy, resulted in significant and clinically meaningful reductions in the annualized rate of moderate and severe exacerbations. These benefits were accompanied by improvements in lung function and patient-reported outcomes, with a safety profile comparable to placebo. For anti-IL-5 strategies, the METREX and METREO studies provided the first pivotal evidence that selective modulation of the eosinophilic pathway can reduce exacerbation risk in COPD. These findings were subsequently reinforced in MATINEE, where further reductions in exacerbations were observed in eosinophil-enriched populations. Collectively, these data strengthen the concept that IL-5 represents a relevant therapeutic target and that identification of pathway activation increases the likelihood of clinical benefit, while also underscoring the biological complexity of COPD and the need for improved stratification tools. GOLD 2026 emphasizes optimization of inhaled therapy, adherence, inhaler technique, and comorbidity management prior to biologic initiation. Because exacerbations critically determine prognosis, their prevention remains the principal therapeutic goal. Biologic therapy represents an important step toward predictive and individualized COPD care, dependent on refined phenotyping and accurate assessment of residual risk.