Osteoarthritis (OA), particularly of the knee, represents a leading cause of chronic pain and functional limitation worldwide. Although pharmacologic therapy remains central to symptom control, real-world treatment effectiveness is frequently compromised by suboptimal medication adherence. To synthesize contemporary evidence on the determinants, clinical consequences, and targeted strategies related to medication nonadherence in osteoarthritis. A narrative review of literature published between January 2021 and February 2026 was conducted using PubMed, Scopus, and supplementary sources. Studies examining determinants of nonadherence, associated outcomes, and adherence-enhancing interventions in OA were thematically integrated. Thirty-nine studies were included. Medication nonadherence in OA is multifactorial, reflecting the interaction of patient-related, therapy-related, and healthcare system determinants. Aging, multimorbidity, cognitive vulnerability, and polypharmacy contribute to unintentional nonadherence, whereas risk perception, safety concerns, and financial barriers frequently drive intentional dose modification or discontinuation. Inconsistent medication use is associated with persistent pain, functional limitation, reduced quality of life, and increased healthcare utilization. Emerging evidence supports patient-centered education, shared decision-making, regimen simplification, pharmacist-led interventions, and digital adherence tools as promising strategies. Medication nonadherence represents a clinically consequential yet underrecognized determinant of treatment effectiveness in osteoarthritis. Addressing adherence through integrated, patient-centered, and system-level strategies is essential to optimizing symptom control, functional outcomes, and healthcare resource utilization in OA populations.