Aromatase inhibitors are class of drugs that inhibit aromatase, a rate limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Estrogens play a vital role in the development and growth of breast tumors especially in postmenopausal women apart from their important functions in cell homeostasis. The reduction of estrogen physiological concentration through aromatase inhibition is one of the most important therapeutic strategies against this cancer type. The third-generation aromatase inhibitors are now used as first-line therapy in the treatment of early and metastatic breast cancer in postmenopausal women. However the quest for new class of drugs still stays indispensable to evade the danger of conceivable rising resistances to existing drugs, toxicity and unwanted side effects due to chronic treatment. The current review deals with recent advances in understanding of aromatase, its mechanism and research in the development of various novel chemotypes as aromatase inhibitors. The new challenges and the fast changing trends in bringing rational approach in aromatase inhibitors to a different level like research in dual/multiple target enzyme inhibition strategies, radiolabeling of aromatase inhibitors as theranostic agents; the development of new computational models for complete understanding of aromatase enzyme and its substrate/ligand interactions will bring in holistic approach to comprehensive inhibition of aromatase and other relevant enzymes for effective treatment and monitoring of postmenopausal breast cancer.