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Purpose: Hyper activation of the HER (erbB) family receptors, HER 1-4, leads to up-regulation of the three vital signalling pathways: mitogen activated protein kinase, phosphoinositide 3-kinase/ AKT, and Janus kinase/ signal transducer and activator of transcription pathways. Blocking HER1/EGFR has a limited anticancer effect due to either secondary mutation e.g., T790M or by-pass signalling of other HER members. The emergence of an anti-panHER approach to blockade of these pathways as a cancer treatment may provide a solution to this resistance. This review aimed to provide an overview of the HER signalling pathways and their involvement in tumour progression and examine the current progress in panHER inhibition.Methods: Recent literature associated with HER signalling pathways and panHER inhibition was reviewed through PubMed and Medline database, followed by critical comparison and analysis.Results: Preclinical studies and clinical trials of panHER inhibitors show promising results, and the potential to improve patient outcomes in solid cancers. Conclusions: The use of panHER inhibitors in cancers with HER family hyper-activation, such as other epithelial cancers and sarcoma, is a new direction to research and has potential in clinical cancer therapy in the future.