In modern medicinal chemistry, the pyridazinone core has emerged as a „versatile“ and privileged scaffold for the design of new therapeutic agents. Over the past decades, numerous pyridazinone derivatives have exhibited significant biological activities across diverse therapeutic areas including antiviral, antimicrobial, cardiovascular, anti-inflammatory, anticancer, and central nervous system disorders. This review discusses the structural diversity, structure-activity relationships (SAR), and pharmacological relevance of pyridazinone-based molecules. Furthermore, it highlights recent advances in hybrid drug design, where the pyridazinone moiety is combined with another pharmacophore to produce synergistic effect that enhance the biological activities of both components towards more than one target. Such hybridization strategy show the potential of pyridazinone scaffold as valuable templates for the development of multifunctional therapeutic agents.