<p>Caffeoylquinic acids (CQAs), commonly referred to as chlorogenic acids, are a structurally diverse group of hydroxycinnamate esters widely distributed in plant-derived foods, medicinal plants, and other botanical matrices. Their diversity arises from the esterification of quinic acid with one or more caffeoyl groups, generating mono-, di-, tri-, and tetra-caffeoylated derivatives with multiple positional isomers. This structural variation strongly influences polarity, stability, chromatographic behavior, natural abundance, and biological interpretation. This review provides an isomer-aware and evidence-based synthesis of CQAs by integrating structural classification, biosynthetic relationships, natural occurrence, isomer-resolved analytical strategies, and structure-dependent bioactivities. Particular attention is given to acyl migration, matrix effects, and analytical challenges that complicate the reliable identification and quantification of closely related CQA isomers. Representative natural concentration values or ranges are also summarized to support the assessment of biological relevance across selected plant-derived matrices. Current evidence indicates that CQAs are associated with antioxidant, anti-inflammatory, antiviral, neuroprotective, anticancer-related, and metabolic regulatory effects. However, these activities should be interpreted according to compound identity, experimental model, applied concentration or dose, control treatment, bioavailability, metabolism, and evidence type. By connecting chemical diversity with analytical rigor and biological evidence, this review highlights current limitations and provides a framework for future isomer-specific studies and the rational evaluation of CQA-containing plant-derived products.</p>