Abstract: Cancer is one of the deadliest diseases involving dysregulated cell proliferation and has been the leading cause of death worldwide. The chemotherapeutic drugs currently used for treating cancer have serious drawbacks of non-specific toxicity and drug resistance. The four members of the human epidermal growth factor receptor (EGFR), namely, ErbB1/HER1, ErbB2/HER2/neu, ErbB3/HER3 and ErbB4/HER4, the trans-membrane family of tyrosine kinase receptors, are overexpressed in many types of cancers. These receptors play an important role in cell proliferation, differentiation, invasion, metastasis and angiogenesis and unregulated activation of cancer cells. Overexpression of ErbB1 and ErbB2 occurs in several types of cancers and is associated with a poor prognosis leading to resistance to ErbB1 directed therapies. Heterodimerization with ErbB2/HER2 is a potent activator of Epidermal Growth Factor Receptor-Tyrosine kinase (EGFRTK) complex than EGFR alone. Though ErbB3/HER3 can bind to a ligand, its kinase domain is devoid of catalytic activity and hence relies on its partner (ErbB2/HER2) for initiation of signals, thus, ErbB2 is involved in the activation of ErbB3. However, recent evidence reveals that ErbB1 and ErbB2 are the most important targets for cancer therapy. By inhibiting these two important kinases, the cancer cell signaling transduction pathways can be inhibited. Lapatinib and monoclonal antibodies like trastuzumab have been used for the dual inhibition of ErbB1 and ErbB2 in the treatment of various cancers. Resistance, however, develops soon. The present report reviews the investigations that have been carried out by earlier workers for targeting ErbB1, ErbB2, and both using small molecules and novel peptides that could help/facilitate researchers to design and develop better cancer chemotherapy.