The use of privileged scaffolds has proven beneficial for generating novel bioactive scaffolds in drug discovery program. Chromone is one such privileged scaffold that has been exploited for designing pharmacologically active analogues. The molecular hybridization technique combines the pharmacophoric features of two or more bioactive compounds to avail a better pharmacological activity in the resultant hybrid analogues. The current review summarizes the rationale and techniques involved in developing hybrid analogues of chromone, which show potential in fields of obesity, diabetes, cancer, Alzheimer’s disease and microbial infections. Here the molecular hybrids of chromone with various pharmacologically active analogues or fragments (donepezil, tacrine, pyrimidines, azoles, furanchalcones, hydrazones, quinolines, etc.) are discussed with their structure-activity relationship against above-mentioned diseases. Detailed methodologies for the synthesis of corresponding hybrid analogues have also been described, with suitable synthetic schemes. The current review will shed light on various strategies utilized for the design of hybrid analogues in the field of drug discovery. The importance of hybrid analogues in various disease conditions is also illustrated. Keywords: Bioactive scaffolds, chromone, drug discovery, molecular hybridization, hybrid analogues.© 2023 Wiley-VCH GmbH.