Attempts to develop a disease modifying intervention for Alzheimer’s disease (AD) through targeting amyloid β (Aβ) have so far been unsuccessful. There is, therefore, a need for novel therapeutics against alternative targets coupled with approaches which may be suitable for early and sustained use likely required for AD prevention. Numerous in vitro and in vivo studies have shown that ﬂavonoids can act within processes and pathways relevant to AD, such as Aβ and tau pathology, increases in BDNF, inﬂammation, oxidative stress and neurogenesis. However, the therapeutic development of ﬂavonoids has been hindered by an ongoing lack of clear mechanistic data that fully takes into consideration metabolism and bioavailability of ﬂavonoids in vivo. With a focus on studies that incorporate these considerations into their experimental design, this review will evaluate the evidence for developing speciﬁc ﬂavonoids as therapeutics for AD. Given the current lack of success of anti-Aβ targeting therapeutics, particular attention will be given to ﬂavonoid-mediated regulation of tau phosphorylation and aggregation, where there is a comparable lack of study. Reﬂecting on this evidence, the obstacles that prevent therapeutic development of ﬂavonoids will be examined. Finally, the signiﬁcance of recent advances in ﬂavonoid metabolomics, modiﬁcations and inﬂuence of the microbiome on the therapeutic capacity of ﬂavonoids in AD are explored. By highlighting the potential of ﬂavonoids to target multiple aspects of AD pathology, as well as considering the hurdles, this review aims to promote the efﬁcient and effective identiﬁcation of ﬂavonoid-based approaches that have potential as therapeutic interventions for AD.