Receptor tyrosine kinases (RTKs) are a superfamily of transmembrane proteins 
that mediate intracellular signaling by phosphorylating substrate proteins 
involved in cell proliferation, survival, differentiation or migration. The 
Human Epidermal growth factor Receptor (HER) family belongs to the RTKs 
superfamily, and comprises four members: EGFR (epidermal growth factor 
receptor), HER2, HER3 and HER4. Physiologically, these receptors are activated 
by the ligands of the EGF family. In solid tumors other mechanisms of 
activation, such as overexpression or molecular alterations have been reported, 
and have been linked to tumour initiation/progression. Because of that, several 
strategies have been developed to target HER receptors and include i) 
antibody-based therapies using monoclonal antibodies against the extracellular 
domain of these receptors, and ii) small molecule tyrosine kinase inhibitors 
(TKIs) against the intracellular kinase domain. In this review we will provide 
basic information about biological aspects of HER receptors and their ligands as 
well as the therapeutic strategies to target them. We also summarize general 
mechanisms of resistance generated in patients to such anti-HER therapies.