Chronic wounds fail to achieve complete closure and are an economic burden to healthcare systems due to the limited treatment options and constant medical attention. Chronic wounds are characterised by dysregulated signalling pathways. Research has focused on naturally derived compounds, stem-cell-based therapy, small molecule drugs, oligonucleotide delivery nanoparticles, exosomes and peptide-based platforms. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT), Wingless-related integration (Wnt)/β-catenin, transforming growth factor-β (TGF-β), nuclear factor erythroid 2–related factor 2 (Nrf2), Notch and hypoxia-inducible factor 1 (HIF-1) signalling pathways have critical roles in wound healing by modulating the inflammatory, proliferative and remodelling phases. Moreover, several regulators of the signalling pathways were demonstrated to be potential treatment targets. In this review, the current research on targeting signalling pathways under chronic wound conditions will be discussed together with implications for future studies.