Epidermal Growth Factor Receptor (EGFR) is a transmembrane glycoprotein that constitutes one of the four members of ErbB family of tyrosine kinase receptors. Activation of EGFR leads to autophosphorylation of receptor tyrosine kinase that initiates a cascade of downstream signaling pathways involved in regulating cellular proliferation, differentiation, and survival. EGFR is abnormally activated by various mechanisms like receptor overexpression, mutation, ligand-dependent receptor dimerization, ligand-independent activation and is associated with the development of variety of human cancers. EGFR inhibition is one of the key targets for cancer chemotherapy. Approval of tyrosine kinase inhibitors such as erlotinib, gefitinib, and lapatinib for the treatment of non-small cell lung cancer led to tremendous development of novel EGFR inhibitors in the last decade. Diverse class of chemical compounds from the synthetic origin has been extensively studied. This review highlights the various classes of synthetically derived molecules which have been reported in the last few years as potential EGFR and EGFR/ErbB-2 dual inhibitors. A brief synthetic methodology to access these compounds has been highlighted along with the SAR. We strongly believe that this review will provide a platform to the synthetic chemists and biologists to design and synthesize new and potent compounds that inhibit EGFR and ErbB-2.